As the population ages, cognitive decline becomes more common. Strategies targeting the gut-brain axis using probiotics are emerging to achieve improvements in neuropsychiatric and neurological disorders. However, the beneficial role of probiotics on brain function in healthy older adults remains unclear. Our aim was to evaluate a multi-species probiotic formulation as a therapeutic approach to reduce emotional and cognitive decline associated with aging in healthy adults. A randomized double-blind placebo-controlled crossover trial was conducted. The study involved a 10-week intervention where participants consumed the assigned probiotic product daily, followed by a 4-week washout period before the second condition started. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and the Psychological Experiments Construction Language Test Battery. At the emotional level, the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) were used. Thirty-three participants, recruited between July 2020 and April 2022, ingested a multispecies probiotic (Lactobacillus rhamnosus and Bifidobacterium lactis). After the intervention, noticeable enhancements were observed in cognitive function (mean difference 1.90, 95% CI 1.09 to 2.70, p < 0.005), memory (mean difference 4.60, 95% CI 2.91 to 6.29, p < 0.005) by MMSE and digit task, and depressive symptoms (mean difference 4.09, 95% CI 1.70 to 6.48, p < 0.005) by BDI. Furthermore, there were significant improvements observed in planning and problem-solving skills, selective attention, cognitive flexibility, impulsivity, and inhibitory ability. Probiotics administration improved cognitive and emotional function in older adults. Limited research supports this, requiring more scientific evidence for probiotics as an effective therapy for cognitive decline. This study has been prospectively registered at ClinicalTrials.gov (NCT04828421; 2020/July/17).

BACKGROUND: Sodium and water retention is a mainstay of the pathophysiology leading to ascites formation in patients with advanced cirrhosis. Refractory ascites denotes the most severe ascites status with limited treatment options and a poor prognosis. We investigated the efficacy and safety of the natriuretic peptide ularitide in patients with refractory cirrhotic ascites.
METHODS: We conducted a randomized placebo-controlled trial investigating ularitide to manage refractory ascites. Until trial termination after interim analyses, we randomized 17 participants in a 2:1 ratio between ularitide (n=11) and placebo (n=6). While hospitalized, the participants received treatment for up to 48 hours. The primary efficacy endpoint was a change in renal water excretion, and secondary end points included changes in renal sodium excretion rate and body weight. The starting dose was 30 ng/kg/min, though later reduced to 20 for safety reasons.
RESULTS: In contrast to the study hypothesis, the mean urine production decreased after 24 hours of ularitide treatment compared with the baseline level (22.8 vs. 47.5 mL/h, p=0.04) and decreased more in participants randomized to ularitide than placebo (24.7 vs. -6.2 mL/h, p=0.05). Ularitide did not increase the renal sodium excretion rate or reduce the weight gain. The incidence rate ratio of adverse reactions in ularitide versus placebo was 8.5 (95% CI: 2-35, p=0.003). Participants treated with ularitide developed serious blood pressure reductions, impacting their renal responsiveness.
CONCLUSIONS: Ularitide in doses of 20-30 ng/kg/min did not benefit urine production and renal sodium excretion rate in patients with refractory ascites. The participants randomized to ularitide overall developed more adverse reactions than placebo. EudraCT no. 2019-002268-28.

Type-2 diabetes mellitus is a frequent comorbidity of cirrhosis independently associated with cirrhosis-related complications and mortality. This post hoc analysis of the ANSWER trial database assessed the effects of long-term human albumin (HA) administration on top of the standard medical treatment (SMT) on the clinical outcomes of a subgroup of 85 outpatients with liver cirrhosis, uncomplicated ascites and insulin-treated diabetes mellitus type 2 (ITDM). Compared to patients in the SMT arm, the SMT + HA group showed a better overall survival (86% vs. 57%, p = .016) and lower incidence rates of paracenteses, overt hepatic encephalopathy, bacterial infections, renal dysfunction and electrolyte disorders. Hospital admissions did not differ between the two arms, but the number of days spent in hospital was lower in the SMT + HA group. In conclusion, in a subgroup of ITDM outpatients with decompensated cirrhosis and ascites, long-term HA administration was associated with better survival and a lower incidence of cirrhosis-related complications.

UNASSIGNED: Bleeding following endoscopic variceal ligation (EVL) may occur as a result of numerous factors, including a diameter of esophageal varices (EV) that is too large to be completely ligated. The present study aimed to develop an artificial intelligence-based endoscopic virtual ruler (EVR) to measure the diameter of EV with a view to finding more suitable cases for EVL.
UNASSIGNED: The present study was a multicenter retrospective study that included a total of 1,062 EVLs in 727 patients with liver cirrhosis with EV, who underwent EVL from April 2016 to March 2023. Patients were divided into early rebleeding (n = 80) and non-rebleeding groups (n = 982) according to whether postoperative bleeding occurred at 6 weeks. The characteristics of patient baseline data, the status of rebleeding at 6 weeks after surgery and the survival status at 6 weeks after rebleeding were analyzed.
UNASSIGNED: The early rebleeding rate following 1,062 EVL procedures was 7.5%, and the mortality rate at 6 weeks after bleeding was 16.5%. Results of the one-way binary logistic regression analysis demonstrated that the risk factors for early rebleeding following EVL included: high TB (P = 0.009), low Alb (P = 0.001), high PT (P = 0.004), PVT (P = 0.026), HCC (P = 0.018), high Child-Pugh score (P < 0.001), Child-Pugh grade C(P < 0.001), high MELD score(P = 0.004), Japanese variceal grade F3 (P < 0.001), diameter of EV (P < 0.001), and number of ligature rings (P = 0.029). Results of the multifactorial binary logistic regression analysis demonstrated that Child-Pugh grade C (P = 0.007), Japanese variceal grade F3 (P = 0.009), and diameter of EV (P < 0.001) may exhibit potential in predicting early rebleeding following EVL. ROC analysis demonstrated that the area under curve (AUC) for EV diameter was 0.848, and the AUC for Japanese variceal grade was 0.635, which was statistically significant (P < 0.001). Thus, results of the present study demonstrated that EV diameter was more optimal in predicting early rebleeding following EVL than Japanese variceal grade criteria. The cut-off value of EV diameter was calculated to be 1.35 cm (sensitivity, 70.0%; specificity, 89.2%).
UNASSIGNED: If the diameter of EV is ≥1.4 cm, there may be a high risk of early rebleeding following EVL surgery; thus, we recommend caution with EVL.

UNASSIGNED: Some recent observational studies have shown that gut microbiota composition is associated with puerperal sepsis (PS) and no causal effect have been attributed to this. The aim of this study was to determine a causal association between gut microbiota and PS by using a two-sample Mendelian randomization (MR) analysis.
UNASSIGNED: This study performed MR analysis on the publicly accessible genome-wide association study (GWAS) summary level data in order to explore the causal effects between gut microbiota and PS. Gut microbiota GWAS (n = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for PS were obtained from the UK Biobank (PS, 3,940 cases; controls, 202,267 cases). Identification of single nucleotide polymorphisms associated with each feature were identified based on a significance threshold of p < 1.0 × 10-5. The inverse variance weighted (IVW) parameter was used as the primary method for MR and it was supplemented by other methods. Additionally, a set of sensitivity analytical methods, including the MR-Egger intercept, Mendelian randomized polymorphism residual and outlier, Cochran\'s Q and the leave-one-out tests were carried out to assess the robustness of our findings.
UNASSIGNED: Our study found 3 species of gut microbiota, Lachnospiraceae FCS020, Lachnospiraceae NK4A136, and Ruminococcaceae NK4A214, to be associated with PS. The IVW method indicated an approximately 19% decreased risk of PS per standard deviation increase with Lachnospiraceae FCS020 (OR = 0.81; 95% CI 0.66-1.00, p = 0.047). A similar trend was also found with Lachnospiraceae NK4A136 (OR = 0.80; 95% CI 0.66-0.97, p = 0.024). However, Ruminococcaceae NK4A214 was positively associated with the risk of PS (OR = 1.33, 95% CI: 1.07-1.67, p = 0.011).
UNASSIGNED: This two-sample MR study firstly found suggestive evidence of beneficial and detrimental causal associations of gut microbiota on the risk of PS. This may provide valuable insights into the pathogenesis of microbiota-mediated PS and potential strategies for its prevention and treatment.

UNASSIGNED: This study was designed to compare the effects of four meal patterns on liver steatosis, fibrosis, and biochemical factors in patients with Nonalcoholic fatty liver disease (NAFLD).
UNASSIGNED: The 12-week intervention was performed on 123 patients with NAFLD who were randomly allocated into four groups: \"3-meals\", \"skipping breakfast\", \"skipping dinner\", and \" 3 meals and 3 snacks per day.\" group. The assessment of liver steatosis, fibrosis, biochemical factors, and anthropometrical evaluation were performed at baseline and at end of the study.
UNASSIGNED: A significant improvement was found in the liver steatosis and fibrosis among the patients who consumed 3 meals, 3 snacks compared to the other groups (P < 0.001). In addition, a higher reduction was observed in serum levels of alanine amino transferase (ALT) (20.93 ± 23.37 mg/dl, P < 0.001), aspartate aminotransferase (AST) (17.15 ± 16.48 mg/dl, P < 0.001), gamma-glutamyl transferase(GGT) (13.43 ± 13.41 mg/dl; P < 0.001), and alkaline phosphatase (ALK) (47.19 ± 60.51 mg/dl; P = 0.004) in patients who consumed 3 meals, 3 snacks, while the concentration of liver enzymes in patients who consumed 3 meals increased significantly. At the end of the study, there was a significant increase in the fasting blood sugar (FBS) concentration in the \"skipping breakfast\" group (17.51 ± 38.85 mg/dl; P = 0.011) and \"3-meals\" group (17.51 ± 38.85 mg/dl, P = 0.03).
UNASSIGNED: Consuming 3 meals, 3 snack per day significantly improves disease severity and biochemical factors in NAFLD patients. Further studies are warranted.
UNASSIGNED: : IRCT20201010048982N2. Name of the registry: Urmia University of Medical Sciences. Date of registration: 2021-08-22, 1400/05/31. URL of trial registry record: https://www.irct.ir/search/result?query=IRCT20201010048982N2.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40200-023-01375-2.

UNASSIGNED: With the COVID-19 pandemic going to be COVID-19 endemic, the negative impact of COVID-19 on the mental health of IBD patients cannot be ignored. This study aimed to investigate the occurrence of anxiety and depression in IBD patients during the COVID-19 pandemic and analyze the factors associated with mental health.
UNASSIGNED: Patients registered at the IBD center were enrolled. Electronic questionnaires about the IBD patient\'s demographic information, basic knowledge of COVID-19, public self-prevention measures, daily life changes, and anxiety and depression were distributed.
UNASSIGNED: Two hundred and fifteen IBD patients finished this study and reported to have anxiety (27%) or depression (34%). During the COVID-19 pandemic, 10.2% of IBD patients reported their diet changes, 58.5% of IBD patients changed their daily physical activities from 3.27 ± 3.252 h to 2.30 ± 2.78 h, 33.7% of IBD patients changed their sleeping duration from 7.99 ± 1.322 h to 8.18 ± 1.447 h. IBD patients\' waiting time for admission (OR: 3.688, 95%CI: 1.003-13.554), regularly oral medicine administration (OR: 18.407, 95%CI: 1.975-171.530) and diet changes (OR: 6.167, 95%CI: 2.158-17.626) were positively correlated with anxiety or depression. IBD patients\' timely periodic infusion of biological agents (OR: 0.586, 95%CI: 0.413-0.830) was negatively correlated with anxiety or depression. IBD patients\' knowledge of COVID-19, public self-prevention, physical activities, and sleep duration changes showed no significant correlation with anxiety and depression, all p values > 0.05.
UNASSIGNED: The main factors of IBD patients\' mental health were diet changes, waiting time for admission, taking oral medicine regularly, and timely periodic infusions of biological agents. Ensuring the supply of routine treatment and medication for IBD patients and establishing systemic online IBD self-management programs would be the focus of major public health events.

Global increases in metabolic disorders such as type 2 diabetes (T2D), especially within Asian populations, highlight the need for novel approaches to dietary intervention. The Tū Ora study previously evaluated the effects on metabolic health of including a nut product into the diet of a New Zealand cohort of Chinese participants with overweight and normoglycaemia or prediabetes through a 12-week randomised, parallel-group clinical trial. In this current study, we compared the impact of this higher-protein nut bar (HP-NB) versus a higher-carbohydrate cereal bar (HC-CB) on the faecal microbiome by employing both 16S rRNA gene amplicon and shotgun metagenomic sequencing of pre- and post-intervention pairs from 84 participants. Despite the higher fibre, protein, and unsaturated fat content of nuts, there was little difference between dietary groups in gut microbiome composition or functional potential, with the bacterial phylum Firmicutes dominating irrespective of diet. The lack of observed change suggests the dietary impact of the bars may have been insufficient to affect the gut microbiome. Manipulating the interplay between the diet, microbiome, and metabolic health may require a more substantial and/or prolonged dietary perturbation to generate an impactful modification of the gut ecosystem and its functional potential to aid in T2D risk reduction.

The immune system is affected by the dietary products humans intake. Immune system regulation by nutrition has uses in the clinical context, but it can also benefit healthy populations by delaying or preventing the emergence of immune-mediated chronic illnesses. In this study, the purpose was to describe and compare the modulator effects on the immune system of the routine ingestion of fresh vs. pasteurized yogurt. A unicentral, prospective, randomized, double-blind, parallel group 8-week nutritional study was carried out comparing the ingestion of 125 g of the products in healthy adults three times a day. A complete battery of in vitro tests on the activity of the immune system, processes and phenomena was performed. Exclusive immune-modulatory effects of fresh yogurt with respect to base line were found in terms of increased systemic IgM (primary immune responses), increased synthesis of IFN-gamma upon stimulation (Th1) and increased peripheral T cells (mainly \"naive\" CD4s). In the three interventions, we observed an increased phagocytic activity and burst test in granulocytes, together with increased secretion of IL-6, IL-1 β and IL-8 (pro-inflammatory) and increased CD16 expression (FcR favoring phagocytosis) in granulocytes. Overall, it is concluded that regardless of bacteria being alive or thermally inactivated, yogurt has common effects on the innate system, but the presence of live bacteria is necessary to achieve a potentiating effect on the specific immune response.

BACKGROUND: Although several epidemiological studies have identified an inverse association between healthy dietary patterns and metabolic dysfunction-associated steatotic liver disease (MASLD)/non-alcoholic fatty liver disease (NAFLD), little is known about the contribution of the food component to MASLD risk and the association between dietary patterns and severity of MASLD. This study aimed to investigate the association between healthy eating patterns and MASLD risk and severity of MASLD.
METHODS: A case-control study including 228 patients diagnosed with MASLD and 228 controls was conducted. The modified Alternate Healthy Eating Index (AHEI), Dietary Approaches to Stop Hypertension (DASH) score, and Alternative Mediterranean Diet (AMED) score were evaluated based on information collected via a validated food-frequency questionnaire. MASLD was confirmed if participants presented with ultrasound-diagnosed fatty liver diseases along with at least one of five cardiometabolic risk factors and no other discernible cause. The logistic regression models were applied to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of MASLD for dietary scores.
RESULTS: Compared with participants in the lowest tertile, those in the highest tertile of AHEI had a 60% reduced risk of MASLD (OR: 0.40; 95% CI: 0.25-0.66). Similar associations were also observed for DASH and AMED, with ORs comparing extreme tertiles of 0.38 (95% CI: 0.22-0.66) and 0.46 (95% CI: 0.28-0.73), respectively. Further Stratified analysis revealed that the inverse associations between AHEI and DASH with MASLD risks were stronger among women than men, and the inverse associations between AMED and MASLD risks were more pronounced among participants with normal weight (OR: 0.22; 95% CI: 0.09-0.49). For components within the dietary score, every one-point increase in vegetable score and whole grain score within the AHEI was associated with an 11% (95% CI: 5-16%) and a 6% (95% CI: 0-12%) lower MASLD risk, respectively. Similar inverse associations with those scores were observed for the DASH and AMED.
CONCLUSIONS: Greater adherence to healthy eating patterns was associated with reduced risk of MASLD, with vegetables and whole grains predominately contributing to these associations. These findings suggested that healthy eating patterns should be recommended for the prevention of MASLD.