Pediatric duodenal cancer and biallelic mismatch repair gene mutations

Gastrointestinal malignancies are extremely rare in the pediatric population, and duodenal cancers represent an even more unusual entity. Intestinal cancers in young adults and children have been observed to be associated with functional deficiencies of the mismatch repair (MMR) system causing a cancer-predisposition syndrome. We report the case of a 16-year-old female with duodenal adenocarcinoma and past history of medulloblastoma found to have a novel germline bialleleic truncating mutation (c.[949C>T]+[949C>T]) of the PMS2 gene. Pediatr Blood Cancer 2009;53:116–120. © 2009 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62997/1/21957_ftp.pd

Fenretinide Treatment Prevents Diet-Induced Obesity in Association With Major Alterations in Retinoid Homeostatic Gene Expression in Adipose, Liver and Hypothalamus

Peer reviewedPublisher PD

Blood Mononuclear Cell Mitochondrial Respiratory Chain Complex IV Activity is Decreased in Multiple Sclerosis Patients: Effects of beta-Interferon Treatment

Objectives: Evidence of mitochondrial respiratory chain (MRC) dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC) MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment. Methods: Spectrophotometric enzyme assay was employed to measure MRC complex IV activity in blood mononuclear cell obtained multiple sclerosis patients and aged matched controls. Results: MRC Complex IV activity was found to be significantly decreased (p < 0.05) in MS patients (2.1 ± 0.8 k/nmol × 10-3; mean ± SD] when compared to the controls (7.2 ± 2.3 k/nmol × 10-3). Complex IV activity in MS patients on β-interferon (4.9 ± 1.5 k/nmol × 10-3) was not found to be significantly different from that of the controls. Conclusions: This study has indicated evidence of peripheral MRC complex IV deficiency in MS patients and has highlighted the potential utility of BMNCs as a potential means to evaluate mitochondrial function in this disorder. Furthermore, the reported improvement of complex IV activity may provide novel insights into the mode(s) of action of β- interferon

Silica Vesicle Nanovaccine Formulations Stimulate Long-Term Immune Responses to the Bovine Viral Diarrhoea Virus E2 Protein

Bovine Viral Diarrhoea Virus (BVDV) is one of the most serious pathogen, which causes tremendous economic loss to the cattle industry worldwide, meriting the development of improved subunit vaccines. Structural glycoprotein E2 is reported to be a major immunogenic determinant of BVDV virion. We have developed a novel hollow silica vesicles (SV) based platform to administer BVDV-1 Escherichia coli-expressed optimised E2 (oE2) antigen as a nanovaccine formulation. The SV-140 vesicles (diameter 50 nm, wall thickness 6 nm, perforated by pores of entrance size 16 nm and total pore volume of 0.934 cm(3)g(-1)) have proven to be ideal candidates to load oE2 antigen and generate immune response. The current study for the first time demonstrates the ability of freeze-dried (FD) as well as non-FD oE2/SV140 nanovaccine formulation to induce long-term balanced antibody and cell mediated memory responses for at least 6 months with a shortened dosing regimen of two doses in small animal model. The in vivo ability of oE2 (100 mu g)/SV-140 (500 mu g) and FD oE2 (100 mu g)/SV-140 (500 mu g) to induce long-term immunity was compared to immunisation with oE2 (100 mu g) together with the conventional adjuvant Quil-A from the Quillaja saponira (10 mu g) in mice. The oE2/SV-140 as well as the FD oE2/SV-140 nanovaccine generated oE2-specific antibody and cell mediated responses for up to six months post the final second immunisation. Significantly, the cell-mediated responses were consistently high in mice immunised with oE2/SV-140 (1,500 SFU/million cells) at the six-month time point. Histopathology studies showed no morphological changes at the site of injection or in the different organs harvested from the mice immunised with 500 mu g SV-140 nanovaccine compared to the unimmunised control. The platform has the potential for developing single dose vaccines without the requirement of cold chain storage for veterinary and human applications

Regulation of growth hormone induced JAK2 and mTOR signalling by hepatic protein tyrosine phosphatase 1B.

Protein tyrosine phosphatase 1B (PTP1B) regulates various signalling pathways including insulin, leptin, IGF-1 and growth hormone (GH) signalling. Transmission of the GH signal depends on Janus kinase 2 (JAK2), which is how PTP1B is thought to modulate GH signalling in the liver, based on studies utilising global PTP1B knockout mice (Ptp1b(-/-)). Here, we investigated the liver-specific role of PTP1B in GH signalling, using liver-specific Ptp1b(-/-) mice (alb-crePtp1b(-/-)), under physiological (chow) or insulin resistant (high-fat diet [HFD]) feeding conditions. Body weight and adiposity were comparable between female alb-crePtp1b(-/-) and Ptp1b(fl/fl) control mice. On chow diet, under 48-hour fasting GH-resistant conditions, GH stimulation in vivo led to a robust stimulation of the JAK-STAT signalling pathway. Alb-crePtp1b(-/-) mice exhibited significantly higher GH-induced JAK2 phosphorylation and SOCS3 gene expression post-GH stimulation. However, STAT3, STAT5 and ERK1/2 phosphorylation and SOCS2 gene expression were similar between groups. Interestingly, GH-induced mTOR phosphorylation was significantly higher in alb-crePtp1b(-/-) mice 5-min post-GH stimulation compared to controls, revealing this part of the pathway under direct control of PTP1B. Under ad lib HFD-fed conditions, GH-induced STAT5 phosphorylation significantly increased in alb-crePtp1b(-/-) mice only, with no alterations in the controls. Overall, our data demonstrate that liver-specific PTP1B deletion leads to significant alterations in GH signalling with increased JAK2, STAT5 and mTOR phosphorylation and SOCS3 gene expression

Effect of periodontal therapy on maxillary sinus mucous membrane thickening in chronic periodontitis: A split-mouth study

Background. This study evaluated the effect of periodontal therapy on mucous membrane thickening in maxillary sinus in chronic periodontitis patients using radiovisiography (RVG) and cone-beam computed tomography (CBCT). Methods. The study population included 30 patients diagnosed with chronic periodontitis, exhibiting bilateral mucosal thickening of maxillary sinus. The selected sites were randomly assigned to group I (control group - not receiving periodontal therapy) and group II (test group - receiving periodontal therapy). The clinical parameters and mucosal thickening of the maxillary sinus were evaluated at baseline and after 9 months. Results. There was a significant decrease in the PPD, CAL as well as mucosal thickening in group II while, group I showed an increase in these parameters. In group II at the end of 9 months the mean mucosal thickening reduction as assessed by CBCT was 0.76±0.18, 0.73±0.24, 0.88±0.42 and 1.13±0.43 mm at the most anterior point (AP), the most posterior point (PP), the mid-point (MP), point of maximum thickness (MT) as well as in the length of the thickened mucosal lining, respectively. Conclusion. The results of our study indicated a reduction in the mucosal thickening of the maxillary sinus after surgical periodontal therapy. The trial was registered with the Clinical Trial Registry of India (Trial REF/ 2016/02/010805)

Definitions of Urinary Tract Infection in Current Research: A Systematic Review

Defining urinary tract infection (UTI) is complex, as numerous clinical and diagnostic parameters are involved. In this systematic review, we aimed to gain insight into how UTI is defined across current studies. We included 47 studies, published between January 2019 and May 2022, investigating therapeutic or prophylactic interventions in adult patients with UTI. Signs and symptoms, pyuria, and a positive urine culture were required in 85%, 28%, and 55% of study definitions, respectively. Five studies (11%) required all 3 categories for the diagnosis of UTI. Thresholds for significant bacteriuria varied from 103 to 105 colony-forming units/mL. None of the 12 studies including acute cystitis and 2 of 12 (17%) defining acute pyelonephritis used identical definitions. Complicated UTI was defined by both host factors and systemic involvement in 9 of 14 (64%) studies. In conclusion, UTI definitions are heterogeneous across recent studies, highlighting the need for a consensus-based, research reference standard for UTI

Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis

Peer reviewedPublisher PD