The Interplay Between Depression, Probiotics, Diet, Immunometabolic Health, the Gut, and the Liver-A Secondary Analysis of the Pro-Demet Randomized Clinical Trial.

(1) Background: Depression, metabolic alternations, and liver diseases are highly comorbid. Studies have shown that probiotics might be helpful in the treatment of the above-mentioned states. The aim of this secondary analysis was to search for possible predictors of probiotics' efficacy on liver-related outcome measures.

Identification of novel 3D-genome altering and complex structural variants underlying retinitis pigmentosa type 17 through a multistep and high-throughput approach.

Introduction: Autosomal dominant retinitis pigmentosa type 17 (adRP, type RP17) is caused by complex structural variants (SVs) affecting a locus on chromosome 17 (chr17q22). The SVs disrupt the 3D regulatory landscape by altering the topologically associating domain (TAD) structure of the locus, creating novel TAD structures (neo-TADs) and ectopic enhancer-gene contacts. Currently, screening for RP17-associated SVs is not included in routine diagnostics given the complexity of the variants and a lack of cost-effective detection methods.

Probiotics may be useful for drug-induced liver dysfunction in patients with depression - A secondary analysis of a randomized clinical trial.

Background & Aims: There is a need to identify new treatment options for depression with its comorbidities. Depression often coexists with liver steatosis and the two may share a pathophysiological overlap, including inflammation and microbiota changes. Probiotics might represent a safe option as an adjunctive therapy in patients with depression and possible liver steatosis.

Metabolic Status Influences Probiotic Efficacy for Depression-PRO-DEMET Randomized Clinical Trial Results.

Probiotics may represent a safe and easy-to-use treatment option for depression or its metabolic comorbidities. However, it is not known whether metabolic features can influence the efficacy of probiotics treatments for depression. This trial involved a parallel-group, prospective, randomized, double-blind, controlled design.

PRO-DEMET Randomized Controlled Trial on Probiotics in Depression-Pilot Study Results.

There is a pressing need to identify new treatment options for depression and its comorbidities. Depression often coexists with metabolic complications, and the two may share a pathophysiological overlap, including inflammation and microbiota changes. Microbiota interventions (e.

The Influence of Probiotic Supplementation on the Severity of Anxiety and Depressive Symptoms; Function and Composition of Gut Microbiota; and Metabolic, Inflammation, and Oxidative Stress Markers in Patients with Depression-A Study Protocol.

This article aims to present the theoretical basis, methodology, and design of a clinical trial we will conduct. The study will be prospective, randomized, placebo-controlled, and double-blind. Each intervention period will last 8 weeks and the trial will be conducted on 100 patients in total, who will be randomly divided into two groups consisting of 50 patients each.

Etiological factors of bloodstream infections in oncological patients, who was hospitalized at the National Institute of Maria Skłodowska-Curie - National Research Institute in Warsaw in 2020-2022.

Aim Of The Study: The purpose of the study was the microbiological analysis of bloodstream infections in patients hospitalized at the National Institute of Oncology, Maria Skłodowska-Curie - National Research Institute in the period from 01/01/2020 to 31/10/2022.

Material And Methods: In the period from 01/01/2020 to 31/10/2022, 18,420 blood cultures obtained from patients hospitalized at the NIO-PIB were analysed in the Department of Clinical Microbiology (total for the presence of bacteria and fungi). Culture for the presence of bacteria was carried out in the BactAlert automatic system by bioMerieux, and for fungi in the Bactec FX automatic system by Becton Dickinson.

The Impact of Diabetes and Glucose-Lowering Therapies on Hepatocellular Carcinoma Incidence and Overall Survival.

Purpose: The incidence of hepatocellular carcinoma (HCC) in the United Kingdom has increased 60% in the past 10 years. The epidemics of obesity and type 2 diabetes are contributing factors. In this article, we examine the impact of diabetes and glucose-lowering treatments on HCC incidence and overall survival (OS).

The Influence of Probiotic Supplementation on Depressive Symptoms, Inflammation, and Oxidative Stress Parameters and Fecal Microbiota in Patients with Depression Depending on Metabolic Syndrome Comorbidity-PRO-DEMET Randomized Study Protocol.

There is a huge need to search for new treatment options and potential biomarkers of therapeutic response to antidepressant treatment. Depression and metabolic syndrome often coexist, while a pathophysiological overlap, including microbiota changes, may play a role. The paper presents a study protocol that aims to assess the effect of probiotic supplementation on symptoms of depression, anxiety and stress, metabolic parameters, inflammatory and oxidative stress markers, as well as fecal microbiota in adult patients with depressive disorders depending on the co-occurrence of metabolic syndrome.

Refeeding syndrome as treatment complication of anorexia nervosa.

Refeeding syndrome (RS) is one of the serious complications during treatment of anorexia nervosa. It includes hormonal and metabolic changes that occur during the process of refeeding in chronically malnourished patient when nutrition is introduced in an excessive and improper amount. RS manifests in water-electrolyte imbalances, including hypophosphatemia (the mostimportant diagnosticmarker), hypokalemia, hyponatremia, hypomagnesaemia, fluid retention, vitamin deficiency and metabolic acidosis.

Accuracy of the European Thyroid Imaging Reporting and Data System (EU-TIRADS) in the valuation of thyroid nodule malignancy in reference to the post-surgery histological results.

Purpose: To assess the clinical usefulness of the European Thyroid Imaging and Reporting Data System (EU-TIRADS) in the valuation of thyroid nodules malignancy in reference to post-surgery histological results.

Material And Methods: Pre-operative ultrasound was performed in consecutive patients admitted for thyroid surgery between June 2017 and January 2018. Thyroid nodules were classified according to EU-TIRADS to five groups: 1-5.

USP7 inhibition alters homologous recombination repair and targets CLL cells independently of ATM/p53 functional status.

The role of deubiquitylase ubiquitin-specific protease 7 (USP7) in the regulation of the p53-dependent DNA damage response (DDR) pathway is well established. Whereas previous studies have mostly focused on the mechanisms underlying how USP7 directly controls p53 stability, we recently showed that USP7 modulates the stability of the DNA damage responsive E3 ubiquitin ligase RAD18. This suggests that targeting USP7 may have therapeutic potential even in tumors with defective p53 or ibrutinib resistance.

T-cell number and subtype influence the disease course of primary chronic lymphocytic leukaemia xenografts in alymphoid mice.

Chronic lymphocytic leukaemia (CLL) cells require microenvironmental support for their proliferation. This can be recapitulated in highly immunocompromised hosts in the presence of T cells and other supporting cells. Current primary CLL xenograft models suffer from limited duration of tumour cell engraftment coupled with gradual T-cell outgrowth.

Targeting the Ataxia Telangiectasia Mutated-null phenotype in chronic lymphocytic leukemia with pro-oxidants.

Inactivation of the Ataxia Telangiectasia Mutated gene in chronic lymphocytic leukemia results in resistance to p53-dependent apoptosis and inferior responses to treatment with DNA damaging agents. Hence, p53-independent strategies are required to target Ataxia Telangiectasia Mutated-deficient chronic lymphocytic leukemia. As Ataxia Telangiectasia Mutated has been implicated in redox homeostasis, we investigated the effect of the Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia genotype on cellular responses to oxidative stress with a view to therapeutic targeting.

Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade.

Purpose: Most patients with hepatocellular carcinoma (HCC) have associated chronic liver disease, the severity of which is currently assessed by the Child-Pugh (C-P) grade. In this international collaboration, we identify objective measures of liver function/dysfunction that independently influence survival in patients with HCC and then combine these into a model that could be compared with the conventional C-P grade.

Patients And Methods: We developed a simple model to assess liver function, based on 1,313 patients with HCC of all stages from Japan, that involved only serum bilirubin and albumin levels.

ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia: data from the UK LRF CLL4 trial.

ATM mutation and BIRC3 deletion and/or mutation have independently been shown to have prognostic significance in chronic lymphocytic leukemia. However, the relative clinical importance of these abnormalities in patients with a deletion of 11q encompassing the ATM gene has not been established. We screened a cohort of 166 patients enriched for 11q-deletions for ATM mutations and BIRC3 deletion and mutation and determined the overall and progression-free survival among the 133 of these cases treated within the UK LRF CLL4 trial.

The role of ATM mutations and 11q deletions in disease progression in chronic lymphocytic leukemia.

Abstract ATM gene alteration is a frequent event in pathogenesis of chronic lymphocytic leukemia (CLL) and occurs as monoallelic loss in the form of 11q23 deletion, with and without mutation in the remaining ATM allele. ATM is a principal DNA damage response gene and biallelic ATM alterations lead to ATM functional loss and chemoresistance. The introduction of new therapies, such as intensive chemoimmunotherapy and inhibition of B-cell receptor (BCR) signaling, has changed clinical responses for the majority of CLL tumors including those with 11q deletion, but it remains to be determined whether these strategies can prevent clonal evolution of tumors with biallelic ATM alterations.

Biallelic ATM inactivation significantly reduces survival in patients treated on the United Kingdom Leukemia Research Fund Chronic Lymphocytic Leukemia 4 trial.

Purpose: The prognostic significance of ATM mutations in chronic lymphocytic leukemia (CLL) is unclear. We assessed their impact in the context of a prospective randomized trial.

Patients And Methods: We analyzed the ATM gene in 224 patients treated on the Leukemia Research Fund Chronic Lymphocytic Leukemia 4 (LRF-CLL4) trial with chlorambucil or fludarabine with and without cyclophosphamide.

ATM germline heterozygosity does not play a role in chronic lymphocytic leukemia initiation but influences rapid disease progression through loss of the remaining ATM allele.

Ataxia telangiectasia patients, with constitutional bi-allelic ATM mutations, have a marked risk of lymphoid tumors and ATM mutation carriers have a smaller risk of cancer. Sporadic ATM mutations occur in 10-20% of chronic lymphocytic leukemia and are often associated with chromosome 11q deletions which cause loss of an ATM allele. The role of constitutional ATM mutations in the pathogenesis of chronic lymphocytic leukemia is unknown.

The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo.

The Ataxia Telangiectasia Mutated (ATM) gene is frequently inactivated in lymphoid malignancies such as chronic lymphocytic leukemia (CLL), T-prolymphocytic leukemia (T-PLL), and mantle cell lymphoma (MCL) and is associated with defective apoptosis in response to alkylating agents and purine analogues. ATM mutant cells exhibit impaired DNA double strand break repair. Poly (ADP-ribose) polymerase (PARP) inhibition that imposes the requirement for DNA double strand break repair should selectively sensitize ATM-deficient tumor cells to killing.

Stratification of pediatric ALL by in vitro cellular responses to DNA double-strand breaks provides insight into the molecular mechanisms underlying clinical response.

The molecular basis of different outcomes in pediatric acute lymphoblastic leukemia (ALL) remains poorly understood. We addressed the clinical significance and mechanisms behind in vitro cellular responses to ionizing radiation (IR)-induced DNA double-strand breaks in 74 pediatric patients with ALL. We found an apoptosis-resistant response in 36% of patients characterized by failure to cleave caspase-3, -7, -9, and PARP1 by 24 hours after IR and an apoptosis-sensitive response with the cleavage of the same substrates in the remaining 64% of leukemias.