Telomere dysfunction instigates inflammation in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition driven by diverse genetic and nongenetic programs that converge to disrupt immune homeostasis in the intestine. We have reported that, in murine intestinal epithelium with telomere dysfunction, DNA damage-induced activation of ataxia-telangiectasia mutated (ATM) results in ATM-mediated phosphorylation and activation of the YAP1 transcriptional coactivator, which in turn up-regulates pro-IL-18, a pivotal immune regulator in IBD pathogenesis. Moreover, individuals with germline defects in telomere maintenance genes experience increased occurrence of intestinal inflammation and show activation of the ATM/YAP1/pro-IL-18 pathway in the intestinal epithelium. Here, we sought to determine the relevance of the ATM/YAP1/pro-IL-18 pathway as a potential driver of IBD, particularly older-onset IBD. Analysis of intestinal biopsy specimens and organoids from older-onset IBD patients documented the presence of telomere dysfunction and activation of the ATM/YAP1/precursor of interleukin 18 (pro-IL-18) pathway in the intestinal epithelium. Employing intestinal organoids from healthy individuals, we demonstrated that experimental induction of telomere dysfunction activates this inflammatory pathway. In organoid models from ulcerative colitis and Crohn's disease patients, pharmacological interventions of telomerase reactivation, suppression of DNA damage signaling, or YAP1 inhibition reduced pro-IL-18 production. Together, these findings support a model wherein telomere dysfunction in the intestinal epithelium can initiate the inflammatory process in IBD, pointing to therapeutic interventions for this disease.

Presence of toxic metals in rice with human health hazards in Tangail district of Bangladesh.

Rice is the staple food of Bangladeshi people and is consumed at least twice a day. Thus, the presence of toxic metals in rice grains has become a major public health concern in Bangladesh. The present research was conducted to investigate the concentrations of toxic metals in rice grains and their possible human health risks in the Tangail district of Bangladesh. Toxic metals were measured by using an inductively coupled plasma mass spectrometer (ICP-MS), and the mean concentrations of toxic metals in rice samples were found in order of Cr > Pb > Ni > As > Cu > Cd. The concentrations of Cr, Pb, As, and Cd in the studied rice grain samples exceeded the FAO/WHO standard values for food samples by 100%, whereas the Ni concentrations by 10%. The principal component analysis (PCA) revealed significant anthropogenic contributions of Cr, Ni, As, and Pb concentrations in rice grains. The metal concentrations in rice grain samples showed strong significant correlations by forming primary clusters with each other. The estimated daily intake (EDI) values of Cr, Ni, As, Cd, and Pb from all samples were higher than the maximum tolerable daily intake (MTDI) allowed. The total targeted hazard quotient (TTHQ) values of Cu, Ni, As, Cd, and Pb also exceeded the threshold value of 1.00, indicating a potential non-carcinogenic risk. The estimated target carcinogenic risk of As was higher than the USEPA threshold level 10-4 (0.0001) indicating increased risk of cancer for adults and children in the study area.

Protein extraction from Saccharomyces cerevisiae at different growth phases.

Saccharomyces cerevisiae is an established model organism with a well characterized genome. However, this model presents a unique problem due to a very resistant cell wall which develops in the late stationary phase resulting in sub-optimal extraction of proteins from such cells using majority of the cell lysis protocols. In this study, several methods from the literature with modifications thereof for lysis of S. cerevisiae cells were analyzed for their suitability for redox proteomics and biological activity studies of both exponential and late stationary phase cultures. The protocols applied are glass bead lysis, sonication, their combinations, alkali extraction, hot-SDS extraction methods and their modifications. The glass bead lysis method showed low yield but could be convenient in cases where in vitro processing steps post extraction is required or if only hydrophilic proteins are of interest. Hot-SDS and alkali extraction protocols yielded higher amount of proteins and these methods are potentially suitable for Western blotting and redox proteomic studies but allow no post-processing treatment(s) on the extracts which may be required for aging- and oxidative stress-related or other studies.

Does increased femoral component size options reduce anterior femoral notching in total knee replacement?

OBJECTIVE: Total knee arthroplasty (TKA) is currently the best option for management of advanced knee arthritis for patients who have exhausted conservative management. There have been significant implant design improvements and this is a continuing process to help the surgeon replicate patient anatomy and kinematics. Amongst the many variables in implantation to achieve a well-functioning TKA, getting optimal femoral component sizing is one. Every implant system has certain discreet implant sizes and the surgeon has to strive to obtain the best fit possible for the patient and attain a well aligned and stable TKA. The aim of this study was to assess the frequency of various femoral component sizes being implanted with a system which has 2.5 mm antero-posterior increment between sizes, and to assess the incidence of anterior femoral notching when using a posterior referencing system. MATERIALS AND METHODS: A retrospective analysis of 739 TKAs implanted in 532 patients between January 2013 and January 2016 at a single center using a single posterior stabilized implant system was done. Patient demographics and femur component size used was obtained from hospital patient records. Immediate post-operative radiographs were analyzed to look for anterior femoral notching and presence of this was classified according to Tayside classification. A telephonic follow up at minimum 2 tears post-surgery was done to interview for occurrence of supracondylar femur fracture or revision for any other causes. RESULTS: There were 207 bilateral and 325 unilateral TKAs performed in 532 patients during the study period. There were 245 males and 287 females with an average age of 61.3 years (43-81 years, SD = 7.2). The most commonly used femoral component was 60 mm and an intermediate size prosthesis was used in 43.11% patients. The incidence of femoral notching ranged from 0 to 6.3%. No patient had sustained a supracondylar condylar fracture at minimum 2 years follow up. CONCLUSION: The availability of a larger number of femoral components in a TKA system allows the surgeon the modularity to choose and obtain the best fit possible. Restoration of posterior condylar offset, preventing anterior notching, medio-lateral overhang and patellofemoral joint stuffing are greatly dependent on correct femoral component sizing. The findings from our study underscore the need to use an implant system with as many femoral size options as possible with lesser increments in between sizes to minimize anterior femoral notching when using a posterior referencing technique.