Can butyrate prevent colon cancer? The AusFAP study: A randomised, crossover clinical trial.

Increased colonic butyrate from microbial fermentation of fibre may protect from colorectal cancer (CRC). Dietary butyrylated high amylose maize starch (HAMSB) delivers butyrate to the large bowel. The objective of this clinical trial (AusFAP) is to evaluate potential chemoprotective effects of HAMSB on polyposis in individuals with a genetic form of colon cancer, Familial Adenomatous Polyposis (FAP).

Effect of EPA on Neonatal Pig Sertoli Cells "": A Possible Treatment to Help Maintain Fertility in Pre-Pubertal Boys Undergoing Treatment With Gonado-Toxic Therapies.

The incidence of cancer in pre-pubertal boys has significantly increased and, it has been recognized that the gonado-toxic effect of the cancer treatments may lead to infertility. Here, we have evaluated the effects on porcine neonatal Sertoli cells (SCs) of three commonly used chemotherapy drugs; cisplatin, 4-Hydroperoxycyclophosphamide and doxorubicin. All three drugs induced a statistical reduction of 5-hydroxymethylcytosine in comparison with the control group, performed by Immunofluorescence Analysis.

Combining conventional and participatory approaches to identify and prioritise management and health-related constraints to smallholder pig production in San Simon, Pampanga, Philippines.

Pork is the main meat produced and consumed in the Philippines. The majority of pigs are raised by smallholders who experience a range of constraints to their pig production. This study presents the findings of the first part of an overarching project that used an Ecohealth approach and aimed to improve the production and competitiveness of the smallholder pig system in an area of the Philippines.

Diagnosis and management of children with Blue Rubber Bleb Nevus Syndrome: A multi-center case series.

Background: Blue Rubber Bleb Nevus Syndrome (BRBNS) is a rare, severe, sporadically occurring disorder characterized by multiple venous malformations.

Aims: To present and analyze a case series of pediatric patients with BRBNS and to describe diagnostic approaches and management options applied.

Patients And Methods: Multicenter, retrospective study, evaluating the diagnosis and management of children with BRBNS.

Crohn's & Colitis Australia inflammatory bowel disease audit: measuring the quality of care in Australia.

Background: Australia has among the highest prevalence of Crohn disease and ulcerative colitis in the world. Management of the chronic gastrointestinal disorders results in significant societal costs and the standard of care is inconsistent across Australia.

Aim: To audit the quality of care received by patients admitted for inflammatory bowel disease (IBD) across Australia against national IBD standards.

Genomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene.

The Eμ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising Eμ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identify frequent disruptive mutations in the PRC1-like component and BCL6-corepressor gene Bcor.

Xenograft of microencapsulated Sertoli cells restores glucose homeostasis in db/db mice with spontaneous diabetes mellitus.

Background: Increased abdominal fat and chronic inflammation in the expanded adipose tissue of obesity contribute to the development of insulin resistance and type 2 diabetes mellitus (T2D). The emerging immunoregulatory and anti-inflammatory properties of Sertoli cells have prompted their application to experimental models of autoimmune/inflammatory disorders, including diabetes. The main goal of this work was to verify whether transplantation of microencapsulated prepubertal porcine Sertoli cells (MC-SC) in the subcutaneous abdominal fat depot of spontaneously diabetic and obese db/db mice (homozygous for the diabetes spontaneous mutation [Lepr ]) would: (i) improve glucose homeostasis and (ii) modulate local and systemic immune response and adipokines profiles.

Long-term stability, functional competence, and safety of microencapsulated specific pathogen-free neonatal porcine Sertoli cells: a potential product for cell transplant therapy.

Background: Porcine Sertoli cells (pSCs) have been employed for cell therapy in pre-clinical studies for several chronic/immune diseases as they deliver molecules associated with trophic and anti-inflammatory effects. To be employed for human xenografts, pSCs products need to comply with safety and stability. To fulfill such requirements, we employed a microencapsulation technology to increase pre-transplant storage stability of specific pathogen-free pSCs (SPF-pSCs) and evaluated the in vivo long-term viability and safety of grafts.

Implications of using on-farm flood flow capture to recharge groundwater and mitigate flood risks along the Kings River, CA.

The agriculturally productive San Joaquin Valley faces two severe hydrologic issues: persistent groundwater overdraft and flooding risks. Capturing flood flows for groundwater recharge could help address both of these issues, yet flood flow frequency, duration, and magnitude vary greatly as upstream reservoir releases are affected by snowpack, precipitation type, reservoir volume, and flood risks. This variability makes dedicated, engineered recharge approaches expensive.

Focal facial dermal dysplasia, type IV, is caused by mutations in CYP26C1.

Focal facial dermal dysplasia (FFDD) Type IV is a rare syndrome characterized by facial lesions resembling aplasia cutis in a preauricular distribution along the line of fusion of the maxillary and mandibular prominences. To identify the causative gene(s), exome sequencing was performed in a family with two affected siblings. Assuming autosomal recessive inheritance, two novel sequence variants were identified in both siblings in CYP26C1-a duplication of seven base pairs, which was maternally inherited, c.

Reversal of experimental Laron Syndrome by xenotransplantation of microencapsulated porcine Sertoli cells.

Recombinant human IGF-1 currently represents the only available treatment option for the Laron Syndrome, a rare human disorder caused by defects in the gene encoding growth hormone receptor, resulting in irreversibly retarded growth. Unfortunately, this treatment therapy, poorly impacts longitudinal growth (13% in females and 19% in males), while burdening the patients with severe side effects, including hypoglycemia, in association with the unfair chore of taking multiple daily injections that cause local intense pain. In this study, we have demonstrated that a single intraperitoneal graft of microencapsulated pig Sertoli cells, producing pig insulin-like growth factor-1, successfully promoted significant proportional growth in the Laron mouse, a unique animal model of the human Laron Syndrome.

Prolongation of skin allograft survival in rats by the transplantation of microencapsulated xenogeneic neonatal porcine Sertoli cells.

Skin rejection remains a major hurdle in skin reconstructive transplantation surgery. In fact, 85% of the grafted patients experience at least one episode of acute skin rejection in the first year. It has been observed that Sertoli cells (SC), when co-transplanted with allo- or xenogeneic cell/tissues, can induce graft acceptance in the absence of systemic immunosuppression.

Functional properties and substrate characterization of human CYP26A1, CYP26B1, and CYP26C1 expressed by recombinant baculovirus in insect cells.

Introduction: The cytochrome P450 CYP26 family of retinoic acid (RA) metabolizing enzymes, comprising CYP26A1, CYP26B1, and CYP26C1 is critical for establishing patterns of RA distribution during embryonic development and retinoid homeostasis in the adult. All three members of this family can metabolize all trans-RA. CYP26C1 has also been shown to efficiently metabolize the 9-cis isomer of RA.

Initial observations of cell-mediated drug delivery to the deep lung.

Using current methodologies, drug delivery to small airways, terminal bronchioles, and alveoli (deep lung) is inefficient, especially to the lower lungs. Urgent lung pathologies such as acute respiratory distress syndrome (ARDS) and post-lung transplantation complications are difficult to treat, in part due to the methodological limitations in targeting the deep lung with high efficiency drug distribution to the site of pathology. To overcome drug delivery limitations inhibiting the optimization of deep lung therapy, isolated rat Sertoli cells preloaded with chitosan nanoparticles were use to obtain a high-density distribution and concentration (92%) of the nanoparticles in the lungs of mice by way of the peripheral venous vasculature rather than the more commonly used pulmonary route.

The role of CYP26 enzymes in defining appropriate retinoic acid exposure during embryogenesis.

Retinoic acid (RA) is a pleiotropic derivative of vitamin A, or retinol, which is responsible for all of the bioactivity associated with this vitamin. The teratogenic influences of vitamin A deficiency and excess RA in rodents were first observed more than 50 years ago. Efforts over the last 15-20 years have refined these observations by defining the molecular mechanisms that control RA availability and signaling during murine embryonic development.

Computer-aided design of microvasculature systems for use in vascular scaffold production.

In vitro biomedical engineering of intact, functional vascular networks, which include capillary structures, is a prerequisite for adequate vascular scaffold production. Capillary structures are necessary since they provide the elements and compounds for the growth, function and maintenance of 3D tissue structures. Computer-aided modeling of stereolithographic (STL) micro-computer tomographic (micro-CT) 3D models is a technique that enables us to mimic the design of vascular tree systems containing capillary beds, found in tissues.

Analysis of Cyp26b1/Rarg compound-null mice reveals two genetically separable effects of retinoic acid on limb outgrowth.

The role of retinoic acid (RA) in limb development is unclear, although it has been suggested to be a proximalizing factor which plays a morphogenetic role in pattern formation. Exogenous RA produces a teratogenic effect on limb morphology; similarly, changes in the endogenous distribution of RA following genetic ablation of the RA-metabolizing enzyme, CYP26B1, result in phocomelia accompanied by changes in expression of proximo-distal (P-D) patterning genes, increased cell death, and delayed chondrocyte maturation. Here we show that disruption of RA receptor (RAR) gamma in a Cyp26b1(-/-) background is able to partially rescue limb skeletal morphology without restoring normal expression of proximo-distal patterning genes.

Cyp26b1 expression in murine Sertoli cells is required to maintain male germ cells in an undifferentiated state during embryogenesis.

In mammals, germ cells within the developing gonad follow a sexually dimorphic pathway. Germ cells in the murine ovary enter meiotic prophase during embryogenesis, whereas germ cells in the embryonic testis arrest in G0 of mitotic cell cycle and do not enter meiosis until after birth. In mice, retinoic acid (RA) signaling has been implicated in controlling entry into meiosis in germ cells, as meiosis in male embryonic germ cells is blocked by the activity of a RA-catabolizing enzyme, CYP26B1.

Fifty years of Australian pediatric gastroenterology.

When the Gastroenterological Society of Australia (GESA) began 50 years ago there were very few pediatric gastroenterologists in the world. The 'Mother' of Paediatric Gastroenterology was Australian Charlotte ('Charlo') Anderson who established one of the world's first pediatric gastroenterology units in Melbourne in the early 1960s. Her earlier work in Birmingham had identified gluten as the component of wheat responsible for celiac disease and helped separate maldigestion (cystic fibrosis) and mucosal malabsorption.

Mycobacterium avium subspecies paratuberculosis in children with early-onset Crohn's disease.

Background: Mycobacterium avium subspecies paratuberculosis (MAP) is the most enduring infectious candidate that may be associated with inflammatory bowel disease (IBD). It is possible that the inconsistencies in the prevalence studies of MAP in adults reflect clinical differences in adult patients studied, including duration of disease and treatment regimens, and also in lack of specificity of some of the assays used. The aim was to determine the presence of MAP in children with symptoms of Crohn's disease (CD) and ulcerative colitis (UC), using gut biopsy tissue and peripheral blood mononuclear cells (PBMC) collected at initial endoscopic examination prior to clinical treatment.

Tulp3 is a critical repressor of mouse hedgehog signaling.

Precise regulation of the morphogen sonic hedgehog (Shh) and modulation of the Shh signaling pathway is required for proper specification of cell fate within the developing limbs and neural tube, and resultant tissue morphogenesis. Tulp3 (tubby-like protein 3) is a protein of unknown function which has been implicated in nervous system development through gene knockout studies. We demonstrate here that mice lacking the Tulp3 gene develop abnormalities of both the neural tube and limbs consistent with improper regulation of Shh signaling.

Micro-CT of corrosion casts for use in the computer-aided design of microvasculature.

Two-dimensional micro-computed tomography (micro-CT) slices can be reconstructed into three-dimensional (3D) models that demonstrate capillary beds. This study focused on the acquisition of data necessary to create scaffolding that directly mimics the unique structural patterns of a microvascular tree system. The Microfil vascular contrasting method was compared to the Baston's methylmethacrylate corrosion casting (BMCC) method to determine which provided the most accurate and high-resolution results for 3D micro-CT reconstruction derived from the two-dimensional micro-CT slices of the capillary beds.

Sertoli cells enhance formation of capillary-like structures in vitro.

Sertoli cells isolated from the testis (referred to as extratesticular Sertoli cells) have been shown to facilitate allo- and xenogeneic cell transplantations. It appears likely that the ability of these cells to enhance the success of cell engraftment is due, in part, to the retention of their intratesticular functions of trophic support and immunoprotection. Sertoli cells also are involved in the regulation of angiogenesis in the testis, which may also contribute to enhanced cell engraftment success facilitated by extratesticular Sertoli cells.

Association between early-life factors and risk of child-onset Crohn's disease among Victorian children born 1983-1998: a birth cohort study.

Background: The incidence of Crohn's disease (CD) with onset before age 16 has increased. Several perinatal characteristics have been associated with CD. Our objective was to examine the temporal change in CD incidence by period of birth and the extent that this could be attributed to perinatal characteristics associated with higher CD risk.