Immunological mechanisms underpinning faecal microbiota transplantation for the treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease that results from a dysregulated immune response against specific environmental triggers in a genetically predisposed individual. Increasing evidence has indicated a causal role for changes in gut microbiota (dysbiosis) contributing to this immune-mediated intestinal inflammation. These mechanisms involve dysregulation of multiple facets of the host immune pathways that are potentially reversible. Faecal microbiota transplantation (FMT) is the transfer of processed stool from a healthy donor into an individual with an illness. FMT has shown promising results in both animal model experiments and clinical studies in IBD in the resolution of intestinal inflammation. The underlying mechanisms, however, are unclear. Insights from these studies have shown interactions between modulation of dysbiosis via changes in abundances of specific members of the gut microbial community and changes in host immunological pathways. Unravelling these causal relationships has promising potential for a translational therapy role to develop targeted microbial therapies and understand the mechanisms that underpin IBD aetiopathogenesis. In this review, we discuss current evidence for the contribution of gut microbiota in the disruption of intestinal immune homeostasis and immunoregulatory mechanisms that are associated with the resolution of inflammation through FMT in IBD.     

Victims of war—Psychoendocrine evidence for the impact of traumatic stress on psychological well-being of adolescents growing up during the Israeli–Palestinian conflict

Violent conflicts are severe traumatic stressors with detrimental effects on physical and mental health, with children and adolescents being particularly at risk. For the hypothalamic–pituitary–adrenal (HPA) axis, characteristic patterns of dysregulation in trauma-exposed individuals have been shown. This study set out to investigate self-reported mental well-being in Palestinian adolescents growing up during the Israeli–Palestinian conflict. Hair cortisol concentrations (HCC) as a psychoendocrine marker for long-term HPA axis aberrations along with the potential protective factor sense of coherence (SoC; i.e., the global mindset to interpret the world and emerging stressors as comprehensible, manageable, and meaningful) were examined. Between 2014 and 2016, posttraumatic stress disorder (PTSD), depression, anxiety, HCC, and SoC were examined in 233 adolescents aged 11 to 16 from the West Bank. More than half of the participants reported trauma exposure, with 40% fulfilling the criteria of a preliminary PTSD diagnosis and a high prevalence of anxiety and depression. HCC was significantly elevated in the PTSD subgroup compared to the subgroup not exposed to any traumatic events (p = 0.046), with trauma-exposed individuals in between. HCC was further associated with typical sequelae of traumatic stress. Notably, SoC was inversely related to self-reported psychopathology, as well as to HCC in the trauma group. The results illustrate the situation of adolescents exposed to chronic traumatic stress and extend the literature on aberrant HPA axis functioning under such conditions. They also point out a central role of SoC, which may imply new strategies to aid individuals exposed to ongoing conflicts.     

Allelic loss on chromosomes 8p, 22q and 18q (DCC) in human prostate cancer

Previous studies have suggested the involvement of tumour-suppressor genes on chromosomes 8p, 22q and 18q (DCC) in prostate cancer. The aim of this study was to further characterize these regions. We investigated 20 polymorphic regions on the 3 chromosome arms in 43 cancers and 10 cases of benign prostatic hyperplasia (BPH). Allelic loss was observed in 72% of cancers on 8p, 16% on 22q and 24% at DCC. For BPH, loss was observed in 20% on 8p and in 12% at DCC. The low incidence of LOH on 22q implies that this locus has no significant role in prostate carcinogenesis. At DCC, although the overall incidence was low, tumours with LOH were mostly of high grade or had metastases, suggesting a role for this gene in prostate cancer progression. On chromosome 8p, 29% of cancers had deletions at the LPL locus on 8p22 and 60% had deletions within a region flanked by the markers D8S339 and ANKI on 8p11.1-p21.1. Within this region, 2 distinct areas of allelic loss were observed, at one or both ANKI and D8S255, and in the region defined by the markers D8S259-D8S505. For the regions 8p22 and ANKI-D8S255, tumours with metastases had a greater frequency of LOH compared to non-metastasizing tumours, suggesting the presence of putative metastasis-suppressor genes in these regions. © 1996 Wiley-Liss, Inc.     

Formulation of re-dispersible dry o/w emulsions using cellulose nanocrystals decorated with metal/metal oxide nanoparticles

This study describes for the first time the preparation of re-dispersible surfactant-free dry eicosane oil emulsion using cellulose nanocrystals (CNCs) using the freeze-drying technique. Surface properties of CNCs constitute a critical point for the stability of o/w emulsions and thus can affect both the droplet size and dispersion properties of the emulsion. Therefore, surface modification of CNCs was performed to understand its effect on the size of the obtained re-dispersible dry o/w eicosane emulsion. Decoration of the CNC surface with metal and metal oxide nanoparticles was conducted through the available alcoholic groups of glycosidic units of CNC, which played a dual role in reducing and stabilizing nanoparticles. Of these nanoparticles, silver (AgNPs), gold (AuNPs), copper oxide (CuO-NPs), and iron oxide (Fe₃O₄-NPs) nanoparticles were prepared via a facile route using alkali activated CNCs. Thorough characterizations pertaining to the as-prepared nanoparticles and their re-dispersible dry eicosane o/w emulsions were investigated using UV-vis spectroscopy, TEM, XRD, particle size, zeta potential, and STEM. Results confirmed the ability of CNCs to stabilize and/or reduce the formed nanoparticles with different sizes and shapes. These nanoparticles showed different shapes and surface charges accompanied by individual morphologies, reflecting on the stability of the re-dispersed dry eicosane emulsions with droplet sizes varying from 1.25 to 0.5 μm.

Schematic diagram for the detailed preparation of dry eicosane o/w emulsions.     

Nonsentinel node metastasis in breast cancer patients: assessment of an existing and a new predictive nomogram

BACKGROUND: The accurate prediction of nonsentinel node (NSN) metastasis in breast cancer patients remains uncertain. METHODS: The medical records of 574 breast cancer patients from 2 different institutions (Mayo Clinic and University of Michigan) with sentinel lymph node biopsy examination and completion axillary lymph node dissection were reviewed for multiple clinicopathologic variables. The Memorial Sloan Kettering Cancer Center nomogram performance for prediction of NSN metastases was assessed. A new model was developed with clinically relevant variables and possible advantages. RESULTS: The Memorial Sloan Kettering Cancer Center nomogram predicted the likelihood of NSN metastasis with an area under the receiver operating characteristic curve of .72 and .86. For predicted probability cut-off points of 5% and 10%, the false-negative rates were 0% and 14% (Mayo), and 17% and 11% (Michigan). A new model was developed with similar area under the curve but lower false-negative rates for low-probability subgroups. CONCLUSIONS: Predictive models for NSN tumor burden are imperfect.     

Nonfunctioning adrenal cortical carcinoma with skeletal muscle metastasis: Case report and imaging at limited resource center

Adrenal cortical carcinoma (ACC) is a rare, aggressive endocrine malignancy with a reported incidence of 1.0-2.0 cases per million population and a poor prognosis due to metastatic spread. About 25% of cases of ACC present with metastases at the time of diagnosis. Metastatic spread of ACC commonly involves lungs, liver, kidney, peritoneum, lymph nodes, venous extension to the renal vein or inferior vena cava and bone. We report a case of a 47-year-old male with a nonfunctioning ACC with metastases to skeletal muscle (subscapularis, paraspinal, iliacus and gluteus maximus muscle) in addition to metastasis to the lung, which was not reported in the literature. Unfortunately, the patient expired prior to the surgery due to respiratory distress.     

Cellulose Nanofibrils as a Damping Material for the Production of Highly Crystalline Nanosized Zeolite Y via Ball Milling

Nanosized zeolite Y is used in various applications from catalysis in petroleum refining to nanofillers in water treatment membranes. Ball milling is a potential and fast technique to decrease the particle size of zeolite Y to the nano range. However, this technique is associated with a significant loss of crystallinity. Therefore, in this study, we investigate the effect of adding biodegradable and recyclable cellulose nanofibrils (CNFs) to zeolite Y in a wet ball milling approach. CNFs are added to shield the zeolite Y particles from harsh milling conditions due to their high surface area, mechanical strength, and water gel-like format. Different zeolite Y to CNFs ratios were studied and compared to optimize the ball milling process. The results showed that the optimal zeolite Y to CNFs ratio is 1:1 to produce a median particle size diameter of 100 nm and crystallinity index of 32%. The size reduction process provided accessibility to the zeolite pores and as a result increased their adsorption capacity. The adsorption capacity of ball-milled particles for methylene blue increased to 29.26 mg/g compared to 10.66 mg/g of the pristine Zeolite. These results demonstrate the potential of using CNF in protecting zeolite Y particles and possibly other micro particles during ball milling.