Nephrology Partnership for Advancing Technology in Healthcare (N-PATH) program: the teachers' perspective.

The N-PATH (Nephrology Partnership for Advancing Technology in Healthcare) program concluded with the 60th European Renal Association 2023 Congress in Milan, Italy. This collaborative initiative aimed to provide advanced training in interventional nephrology to young European nephrologists. Funded by Erasmus+ Knowledge Alliance, N-PATH addressed the global burden of chronic kidney disease (CKD) and the shortage of nephrologists. CKD affects >850 million people worldwide, yet nephrology struggles to attract medical talent, leading to unfilled positions in residency programs. To address this, N-PATH focused on enhancing nephrology education through four specialized modules: renal expert in renal pathology (ReMAP), renal expert in vascular access (ReVAC), renal expert in medical ultrasound (ReMUS) and renal expert in peritoneal dialysis (RePED). ReMAP emphasized the importance of kidney biopsy in nephrology diagnosis and treatment, providing theoretical knowledge and hands-on training. ReVAC centred on vascular access in haemodialysis, teaching trainees about different access types, placement techniques and managing complications. ReMUS recognized the significance of ultrasound in nephrology, promoting interdisciplinary collaboration and preparing nephrologists for comprehensive patient care. RePED addressed chronic peritoneal dialysis, offering comprehensive training in patient selection, prescription, monitoring, complications and surgical techniques for catheter insertion. Overall, N-PATH's strategy involved collaborative networks, hands-on training, mentorship, an interdisciplinary approach and the integration of emerging technologies. By bridging the gap between theoretical knowledge and practical skills, N-PATH aimed to revitalize interest in nephrology and prepare proficient nephrologists to tackle the challenges of kidney diseases. In conclusion, the N-PATH program aimed to address the shortage of nephrologists and improve the quality of nephrology care in Europe. By providing specialized training, fostering collaboration and promoting patient-centred care, N-PATH aimed to inspire future nephrology professionals to meet the growing healthcare demands related to kidney diseases and elevate the specialty's status within the medical community.

Verbal lie detection using Large Language Models.

Human accuracy in detecting deception with intuitive judgments has been proven to not go above the chance level. Therefore, several automatized verbal lie detection techniques employing Machine Learning and Transformer models have been developed to reach higher levels of accuracy. This study is the first to explore the performance of a Large Language Model, FLAN-T5 (small and base sizes), in a lie-detection classification task in three English-language datasets encompassing personal opinions, autobiographical memories, and future intentions. After performing stylometric analysis to describe linguistic differences in the three datasets, we tested the small- and base-sized FLAN-T5 in three Scenarios using 10-fold cross-validation: one with train and test set coming from the same single dataset, one with train set coming from two datasets and the test set coming from the third remaining dataset, one with train and test set coming from all the three datasets. We reached state-of-the-art results in Scenarios 1 and 3, outperforming previous benchmarks. The results revealed also that model performance depended on model size, with larger models exhibiting higher performance. Furthermore, stylometric analysis was performed to carry out explainability analysis, finding that linguistic features associated with the Cognitive Load framework may influence the model's predictions.

Assessment and management of heart failure in patients with chronic kidney disease.

Heart failure (HF) and chronic kidney disease (CKD) are two pathological conditions with a high prevalence in the general population. When they coexist in the same patient, a strict interplay between them is observed, such that patients affected require a clinical multidisciplinary and personalized management. The diagnosis of HF and CKD relies on signs and symptoms of the patient but several additional tools, such as blood-based biomarkers and imaging techniques, are needed to clarify and discriminate the main characteristics of these diseases. Improved survival due to new recommended drugs in HF has increasingly challenged physicians to manage patients with multiple diseases, especially in case of CKD. However, the safe administration of these drugs in patients with HF and CKD is often challenging. Knowing up to which values ​​of creatinine or renal clearance each drug can be administered is fundamental. With this review we sought to give an insight on this sizable and complex topic, in order to get clearer ideas and a more precise reference about the diagnostic assessment and therapeutic management of HF and CKD.

Chemopreventive effect of a milk whey by-product derived from Buffalo (Bubalus bubalis) in protecting from colorectal carcinogenesis.

BACKGROUND: Several studies show that natural foods are a source of compounds with anticancer properties that affect the gut microbiota and its metabolites. In the present study, we investigate the effect of a delactosed buffalo milk whey by-product (DMW) on colorectal carcinogenesis. METHODS: The effect of DMW on colorectal carcinoma (CRC) was investigated in the established mouse model of azoxymethane (AOM)-induced colon carcinoma, which closely resembles the human clinical condition of CRC. The effect of DMW on CRC immortalized cell lines was also evaluated to further identify the antineoplastic mechanism of action. RESULTS: Pretreatment of AOM-treated mice with DMW significantly (P < 0.05) reduced the percentage of mice bearing both aberrant crypt foci with more than four crypts (which are early precancerous lesions that progress to CRC) and tumors. In addition, DMW completely counteracted the effect of AOM on protein expression of caspase-9, cleaved caspase-3 and poly ADP-ribose polymerase in colonic tissue. Administration of DMW alone (i.e. without AOM) resulted in changes in the composition of the gut microbiota, leading to enrichment or depletion of genera associated with health and disease, respectively. DMW was also able to restore AOM-induced changes in specific genera of the gut microbiota. Specifically, DMW reduced the genera Atopobiaceae, Ruminococcus 1 and Lachnospiraceae XPB1014 and increased the genera Parabacteroides and Candidatus Saccharimonas, which were increased and reduced, respectively, by AOM. Blood levels of butyric acid and cancer diagnostic markers (5-methylcytidine and glycerophosphocholine), which were increased by AOM treatment, were reduced by DMW. Furthermore, DMW exerted cytotoxic effects on two human CRC cell lines (HCT116 and HT29) and these effects were associated with the induction of apoptotic signaling. CONCLUSIONS: Our results suggest that DMW exerts chemopreventive effects and restores the gut microbiota in AOM-induced CRC, and induces cytotoxic effect on CRC cells. DMW could be an important dietary supplement to support a healthy gut microbiota and reduce the prevalence of CRC in humans. Video Abstract.

Quantitative ADC: An Additional Tool in the Evaluation of Prostate Cancer?

Prostate cancer is one of the most common tumors among the male population. Magnetic resonance imaging (MRI), standardized by the PI-RADS version 2.1 scoring system, has a fundamental role in detecting prostate cancer and evaluating its aggressiveness. Diffusion-weighted imaging sequences and apparent diffusion coefficient values, in particular, are considered fundamental for the detection and characterization of lesions. In 2016 the International Society of Urological Pathology introduced a new anatomopathological 5-grade scoring system for prostate cancer. The aim of this study is to evaluate the correlation between quantitative apparent diffusion coefficient values (ADC) derived from diffusion-weighted imaging (DWI) sequences and the International Society of Urological Pathology (ISUP) and PI-RADS groups. Our retrospective study included 143 patients with 154 suspicious lesions, observed on prostate magnetic resonance imaging and compared with the histological results of the biopsy. We observed that ADC values can aid in discriminating between not clinically significant (ISUP 1) and clinically significant (ISUP 2-5) prostate cancers. In fact, ADC values were lower in ISUP 5 lesions than in negative lesions. We also found a correlation between ADC values and PI-RADS groups; we noted lower ADC values in the PI-RADS 5 and PI-RADS 4 groups than in the PI-RADS 3 group. In conclusion, quantitative apparent diffusion coefficient values can be useful to assess the aggressiveness of prostate cancer.

Immunosuppressive treatment for autoimmune blistering diseases does not impair production of neutralizing antibodies after "booster" dose of COVID-19 vaccine.

Since vaccines against COVID-19 are available, it has been debated if immunosuppressed patients with autoimmune blistering diseases (AIBDs) should be advised to interrupt the immunosuppressive therapy before receiving the vaccine, with consequent risk to experience a flare of disease. In the present study, we measured the neutralizing antibodies production after anti-SARS-CoV-2 vaccination in patients with AIBDs on immunosuppressive treatment, compared to healthy controls. Our results give strength to the hypothesis that these patients do not need to discontinue their therapy to produce effective levels of neutralizing antibodies, in other words to achieve successful protection.

High Amylose Wheat Bread at Breakfast Increases Plasma Propionate Concentrations and Reduces the Postprandial Insulin Response to the Following Meal in Overweight Adults.

BACKGROUND: High amylose starchy foods modulate the postprandial metabolic response in humans. However, the mechanisms of their metabolic benefits and their impact on the subsequent meal have not been fully elucidated. OBJECTIVE: We aimed to evaluate whether glucose and insulin responses to a standard lunch are influenced by the consumption of amylose-rich bread at breakfast in overweight adults and whether changes in plasma short chain fatty acids (SCFAs) concentrations contribute to their metabolic effects. METHODS: Using a randomized crossover design, 11 men and 9 women, BMI 30 ± 3 kg/m2, 48 ± 19 y, consumed at breakfast 2 breads made with high amylose flour (HAF): 85%-HAF (180 g) and 75%-HAF (170 g), and control bread (120 g) containing 100% conventional flour. Plasma samples were collected at fasting, 4 h after breakfast, and 2 h after a standard lunch to measure glucose, insulin, and SCFA concentrations. ANOVA posthoc analyses were used for comparisons. RESULTS: Postprandial plasma glucose responses were 27% and 39% lower after breakfasts with 85%- and 70%-HAF breads than control bread (P = 0.026 and P = 0.003, respectively), with no difference after lunch. Insulin responses were not different between the 3 breakfasts, whereas there was a 28% lower response after the lunch following breakfast with 85%-HAF bread than the control (P = 0.049). Propionate concentrations increased from fasting by 9% and 12% 6 h after breakfasts with 85%- and 70%-HAF breads and decreased by 11% with control bread (P < 0.05). At 6 h after breakfast with 70%-HAF bread, plasma propionate and insulin were inversely correlated (r = -0.566; P = 0.044). CONCLUSIONS: Amylose-rich bread reduces the postprandial glucose response after breakfast and insulin concentrations after the subsequent lunch in overweight adults. This second meal effect may be mediated by the elevation of plasma propionate due to intestinal fermentation of resistant starch. High amylose products could be a promising tool in a dietary prevention strategy for type 2 diabetes. THIS TRIAL WAS REGISTERED AT CLINICAL TRIAL REGISTRY AS: NCT03899974 (https://www. CLINICALTRIALS: gov/ct2/show/NCT03899974).

Targeting gut dysbiosis against inflammation and impaired autophagy in Duchenne muscular dystrophy.

Nothing is known about the potential implication of gut microbiota in skeletal muscle disorders. Here, we provide evidence that fecal microbiota composition along with circulating levels of short-chain fatty acids (SCFAs) and related metabolites are altered in the mdx mouse model of Duchenne muscular dystrophy (DMD) compared with healthy controls. Supplementation with sodium butyrate (NaB) in mdx mice rescued muscle strength and autophagy, and prevented inflammation associated with excessive endocannabinoid signaling at CB1 receptors to the same extent as deflazacort (DFZ), the standard palliative care for DMD. In LPS-stimulated C2C12 myoblasts, NaB reduces inflammation, promotes autophagy, and prevents dysregulation of microRNAs targeting the endocannabinoid CB1 receptor gene, in a manner depending on the activation of GPR109A and PPARγ receptors. In sum, we propose a novel disease-modifying approach in DMD that may have benefits also in other muscular dystrophies.

The Hepatic Mitochondrial Alterations Exacerbate Meta-Inflammation in Autism Spectrum Disorders.

The role of the liver in autism spectrum disorders (ASD), developmental disabilities characterized by impairments in social interactions and repetitive behavioral patterns, has been poorly investigated. In ASD, it has been shown a dysregulation of gut-brain crosstalk, a communication system able to influence metabolic homeostasis, as well as brain development, mood and cognitive functions. The liver, with its key role in inflammatory and metabolic states, represents the crucial metabolic organ in this crosstalk. Indeed, through the portal vein, the liver receives not only nutrients but also numerous factors derived from the gut and visceral adipose tissue, which modulate metabolism and hepatic mitochondrial functions. Here, we investigated, in an animal model of ASD (BTBR mice), the involvement of hepatic mitochondria in the regulation of inflammatory state and liver damage. We observed increased inflammation and oxidative stress linked to hepatic mitochondrial dysfunction, steatotic hepatocytes, and marked mitochondrial fission in BTBR mice. Our preliminary study provides a better understanding of the pathophysiology of ASD and could open the way to identifying hepatic mitochondria as targets for innovative therapeutic strategies for the disease.

Maternal treatment with sodium butyrate reduces the development of autism-like traits in mice offspring.

Several studies indicate a relationship between maternal gut microbiota alteration and increased risk of autism spectrum disorders (ASD) in offspring. The possibility of compensating for such metabolic dysfunction at a very early stage of disease via maternal treatment has not been enough explored. Here, we examined in BTBR mouse model of ASD the effect of maternal treatment with the gut microbial metabolite butyrate (BUT) on the behavioral and synaptic plasticity deficits in juvenile and adult offspring. We show that BUT treatment of BTBR dams rescues the social and partially the repetitive behavior deficits in the offspring. In addition, maternal BUT implementation prevents the cerebellar cortex hypertrophy as well as the Purkinje cells firing and long-term synaptic plasticity deficits in BTBR mice. Our results demonstrate, for the first time, that maternal BUT treatment can improve ASD-like symptoms in offspring thus providing new directions for the early treatment of neurodevelopmental disorders.

Phaseolus vulgaris extract ameliorates high-fat diet-induced colonic barrier dysfunction and inflammation in mice by regulating peroxisome proliferator-activated receptor expression and butyrate levels.

Obesity is a health concern worldwide, and its onset is multifactorial. In addition to metabolic syndrome, a high-fat diet induces many deleterious downstream effects, such as chronic systemic inflammation, a loss of gut barrier integrity, and gut microbial dysbiosis, with a reduction of many butyrate-producing bacteria. These conditions can be ameliorated by increasing legumes in the daily diet. White and kidney beans (Phaseolus vulgaris L.) and their non-nutritive bioactive component phaseolamin were demonstrated to mitigate several pathological features related to a metabolic syndrome-like condition. The aim of the present study was to investigate the molecular pathways involved in the protective effects on the intestinal and liver environment of a chronic oral treatment with P. vulgaris extract (PHAS) on a murine model of the high-fat diet. Results show that PHAS treatment has an anti-inflammatory effect on the liver, colon, and cecum. This protective effect was mediated by peroxisome proliferator-activated receptor (PPAR)-α and γ. Moreover, we also observed that repeated PHAS treatment was able to restore tight junctions' expression and protective factors of colon and cecum integrity disrupted in HFD mice. This improvement was correlated with a significant increase of butyrate levels in serum and fecal samples compared to the HFD group. These data underline that prolonged treatment with PHAS significantly reduces some pathological features related to the metabolic syndrome-like condition, such as inflammation and intestinal barrier disruption; therefore, PHAS could be a valid tool to be associated with the therapeutic strategy.

The Beneficial Effects of Ultramicronized Palmitoylethanolamide in the Management of Neuropathic Pain and Associated Mood Disorders Induced by Paclitaxel in Mice.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication of antineoplastic drugs, particularly paclitaxel (PTX). It can affect the quality of patients' lives and increase the risk of developing mood disorders. Although several drugs are recommended, they yielded inconclusive results in clinical trials. The aim of the present work is to investigate whether the palmitoylethanolamide (PEA) would reduce PTX-induced CIPN and associated mood disorders. Moreover, the role PPAR-α and the endocannabinoid system will also be investigated. CIPN was induced by intraperitoneally injection of PTX (8 mg/kg) every other day for a week. PEA, 30 mg/kg, was orally administrated in a bioavailable form (i.e., ultramicronized PEA, um-PEA) one hour after the last PTX injection, for 7 days. In the antagonism experiments, AM281 (1 mg/kg) and GW6471 (2 mg/kg) were administrated 30 min before um-PEA. Our results demonstrated that um-PEA reduced the development of hypersensitivity with the effect being associated with the reduction in spinal and hippocampal pro-inflammatory cytokines, as well as antidepressive and anxiolytic effects. Moreover, the PPAR-α and CB1 receptor antagonists blocked the behavioral and antinociceptive effects of um-PEA. Our findings suggest that um-PEA is a promising adjunct in CIPN and associated mood disorders through the activation of PPAR-α, which influences the endocannabinoid system.

Therapeutic effects elicited by the probiotic Lacticaseibacillus rhamnosus GG in children with atopic dermatitis. The results of the ProPAD trial.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% of the pediatric population associated with alteration of skin and gut microbiome. Probiotics have been proposed for AD treatment. The ProPAD study aimed to investigate the therapeutic effects of the probiotic Lacticaseibacillus rhamnosus GG (LGG) in children with AD. METHODS: In total, 100 AD patients aged 6-36 months were enrolled in a randomized, double-blind, controlled trial to receive placebo (Group A) or LGG (1 x 1010 CFU/daily) (Group B) for 12 weeks. The primary outcome was the evaluation of the efficacy of LGG supplementation on AD severity comparing the Scoring Atopic Dermatitis (SCORAD) index at baseline (T0) and at 12-week (T12). A reduction of ≥8.7 points on the SCORAD index was considered as minimum clinically important difference (MCID). The secondary outcomes were the SCORAD index evaluation at 4-week (T16) after the end of LGG treatment, number of days without rescue medications, changes in Infant Dermatitis Quality Of Life questionnaire (IDQOL), gut microbiome structure and function, and skin microbiome structure. RESULTS: The rate of subjects achieving MCID at T12 and at T16 was higher in Group B (p < .05), and remained higher at T16 (p < .05)The number of days without rescue medications was higher in Group B. IDQOL improved at T12 in the Group B (p < .05). A beneficial modulation of gut and skin microbiome was observed only in Group B patients. CONCLUSIONS: The probiotic LGG could be useful as adjunctive therapy in pediatric AD. The beneficial effects on disease severity and quality of life paralleled with a beneficial modulation of gut and skin microbiome.

[Peritoneal Dialysis in Italy: the 7th GSDP-SIN census 2019].

Objectives: Analysis of the results of the 7th National Census (Cs-19) of Peritoneal Dialysis in Italy, conducted in 2020-21 by the Peritoneal Dialysis Project Group of the Italian Society of Nephrology, for the year 2019. Materials and methods: The data was initially collected using specially designed software, which after entering the data of individual patients allows the aggregate extraction of the necessary information. The difficulties due to the COVID pandemic made it necessary to also use the traditional on-line questionnaire used previously. Of the 237 Centers envisaged, 198 responded, of which 177 with complete data for HD also in 2016. Results: Overall incidence and prevalence (31/12/2019) were respectively 1,363 (CAPD/APD = 741/622) and 3,922 (CAPD/APD = 1,857 / 2,065) patients. The percentage incidence and prevalence (177 Centers) decreased compared to 2016, respectively, from 23.8% to 22.1% and from 17.3% to 16.6%. 31.4% started PD incrementally in 60.3% of the Centers. The catheter is placed by the Nephrologist alone in 19.7%. Assisted PD is used by 24.5% of the prevalent patients, mostly (83.8%) by a family member. In 2019, the exit from PD (ep/100 years-pts: 11.6 in HD; 8.9 death; 6.0 Tx) is decreasing for all causes. The main cause of transfer to HD remains peritonitis (26.8%). The incidence of peritonitis in 2019 dropped further to 0.190 ep/year-pts as well as the incidence of new cases of EPS (0.103 ep/100 years-pts). Conclusions: The Cs-19 confirms the good results of the DP in Italy.