Assessment of sensorineural hearing loss in well controlled and poorly controlled patients with diabetes mellitus

Background: The prevalence of diabetes and its adverse effects have snowballed through the world due to changes in lifestyle. Association of diabetes with hearing loss has been a topic of discussion for many years. Aim and Objectives: To assess the Sensorineural Hearing Loss (SNHL) in patients with diabetes and correlate it with the duration and severity of hyperglycemia. Material and Methods: This hospital based cross-sectional study was carried out from August 2017 to July 2018 among 100 patients with diabetes aged between 31-60 years. Patients were grouped as per age, duration of Diabetes Mellitus (DM) and glycaemic control using HbA1c levels. The results were statistically analysed using Chi-square test and Pearson's coefficient to draw significance. Results: The incidence of SNHL in patients with diabetes was 79% and the correlation among different age group showed statistical significance (p < 0.05). There was no statistical association between the gender and hearing loss among patients with diabetes (p = 0.70). However, association of SNHL to the duration of DM was statistically significant when compared among all three duration groups. No statistical correlation was present with the glycaemic control of DM. Results showed high frequency SNHL with 41.8% patients with diabetes having moderate degree of hearing loss. Conclusion: Early referral for hearing assessment in patients with diabetes can be followed by clinicians aiming at improving quality of life with timely measures

A DNMT3B Alternatively Spliced Exon and Encoded Peptide Are Novel Biomarkers of Human Pluripotent Stem Cells

A major obstacle in human stem cell research is the limited number of reagents capable of distinguishing pluripotent stem cells from partially differentiated or incompletely reprogrammed derivatives. Although human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) express numerous alternatively spliced transcripts, little attention has been directed at developing splice variant-encoded protein isoforms as reagents for stem cell research. In this study, several genes encoding proteins involved in important signaling pathways were screened to detect alternatively spliced transcripts that exhibited differential expression in pluripotent stem cells (PSCs) relative to spontaneously differentiated cells (SDCs). Transcripts containing the alternatively spliced exon 10 of the de novo DNA methyltransferase gene, DNMT3B, were identified that are expressed in PSCs. To demonstrate the utility and superiority of splice variant specific reagents for stem cell research, a peptide encoded by DNMT3B exon 10 was used to generate an antibody, SG1. The SG1 antibody detects a single DNMT3B protein isoform that is expressed only in PSCs but not in SDCs. The SG1 antibody is also demonstrably superior to other antibodies at distinguishing PSCs from SDCs in mixed cultures containing both pluripotent stem cells and partially differentiated derivatives. The tightly controlled down regulation of DNMT3B exon 10 containing transcripts (and exon 10 encoded peptide) upon spontaneous differentiation of PSCs suggests that this DNMT3B splice isoform is characteristic of the pluripotent state. Alternatively spliced exons, and the proteins they encode, represent a vast untapped reservoir of novel biomarkers that can be used to develop superior reagents for stem cell research and to gain further insight into mechanisms controlling stem cell pluripotency

92-Gene Molecular Profiling in Identification of Cancer Origin: A Retrospective Study in Chinese Population and Performance within Different Subgroups

BACKGROUND: After cancer diagnosis, therapy for the patient is largely dependent on the tumor origin, especially when a metastatic tumor is being treated. However, cases such as untypical metastasis, poorly differentiated tumors or even a limited number of tumor cells may lead to challenges in identifying the origin. Moreover, approximately 3% to 5% of total solid tumor patients will not have to have their tumor origin identified in their lifetime. The THEROS CancerTYPE ID® is designed for identifying the tumor origin with an objective, rapid and standardized procedure. METHODOLOGY AND PRINCIPAL FINDINGS: This is a blinded retrospective study to evaluate performance of the THEROS CancerTYPE ID® in a Chinese population. In total, 184 formalin-fixed paraffin-embedded (FFPE) samples of 23 tumor origins were collected from the tissue bank of Fudan University Shanghai Cancer Center (FDUSCC). A standard tumor cell enrichment process was used, and the prediction results were compared with reference diagnosis, which was confirmed by two experienced pathologists at FDUSCC. All of the 184 samples were successfully analyzed, and no tumor specimens were excluded because of sample quality issues. In total, 151 samples were correctly predicted. The agreement rate was 82.1%. A Pearson Chi-square test shows that there is no difference between this study and the previous evaluation test performed by bioTheranostics Inc. No statistically significant decrease was observed in either the metastasis group or tumors with high grades. CONCLUSIONS: A comparable result with previous work was obtained. Specifically, specimens with a high probability score (>0.85) have a high chance (agreement rate = 95%) of being correctly predicted. No performance difference was observed between primary and metastatic specimens, and no difference was observed among three tumor grades. The use of laser capture micro-dissection (LCM) makes the THEROS CancerTYPE ID® accessible to almost all of the cancer patients with different tumor statuses

Bordetella pertussis Autotransporter Vag8 Binds Human C1 Esterase Inhibitor and Confers Serum Resistance

Bordetella pertussis employs numerous strategies to evade the immune system, including the ability to resist killing via complement. Previously we have shown that B. pertussis binds a complement regulatory protein, C1 esterase inhibitor (C1inh) to its surface in a Bvg-regulated manner (i.e. during its virulence phase), but the B. pertussis factor was not identified. Here we set out to identify the B. pertussis C1inh-binding factor. Using a serum overlay assay, we found that this factor migrates at approximately 100 kDa on an SDS-PAGE gel. To identify this factor, we isolated proteins of approximately 100 kDa from wild type strain BP338 and from BP347, an isogenic Bvg mutant that does not bind C1inh. Using mass spectrometry and bioinformatics, we identified the autotransporter protein Vag8 as the putative C1inh binding protein. To prove that Vag8 binds C1inh, vag8 was disrupted in two different B. pertussis strains, namely BP338 and 18–323, and the mutants were tested for their ability to bind C1inh in a surface-binding assay. Neither mutant strain was capable of binding C1inh, whereas a complemented strain successfully bound C1inh. In addition, the passenger domain of Vag8 was expressed and purified as a histidine-tagged fusion protein and tested for C1inh-binding in an ELISA assay. Whereas the purified Vag8 passenger bound C1inh, the passenger domain of BrkA (a related autotransporter protein) failed to do so. Finally, serum assays were conducted to compare wild type and vag8 mutants. We determined that vag8 mutants from both strains were more susceptible to killing compared to their isogenic wild type counterparts. In conclusion, we have discovered a novel role for the previously uncharacterized protein Vag8 in the immune evasion of B. pertussis. Vag8 binds C1inh to the surface of the bacterium and confers serum resistance

Search for a Technicolor omega_T Particle in Events with a Photon and a b-quark Jet at CDF

If the Technicolor omega_T particle exists, a likely decay mode is omega_T -> gamma pi_T, followed by pi_T -> bb-bar, yielding the signature gamma bb-bar. We have searched 85 pb^-1 of data collected by the CDF experiment at the Fermilab Tevatron for events with a photon and two jets, where one of the jets must contain a secondary vertex implying the presence of a b quark. We find no excess of events above standard model expectations. We express the result of an exclusion region in the M_omega_T - M_pi_T mass plane.Comment: 14 pages, 2 figures. Available from the CDF server (PS with figs): http://www-cdf.fnal.gov/physics/pub98/cdf4674_omega_t_prl_4.ps FERMILAB-PUB-98/321-

The effect of sepsis and its inflammatory response on mechanical clot characteristics: a prospective observational study

Purpose: Sepsis and its progression are known to have a major influence on the coagulation system. Current coagulation tests are of limited use when assessing coagulation in sepsis patients. This study aims to assess the potential for a new functional biomarker of clot microstructure, fractal dimension, to identify changes in the mechanical properties of clot microstructure across the sepsis spectrum (sepsis, severe sepsis and septic shock). Methods: A total of 100 patients that presented acutely to a large teaching hospital were included in this prospective observational study (50 sepsis, 20 severe sepsis and 30 septic shock) against a matched control of 44 healthy volunteers. Fractal analysis was performed, as well as standard markers of coagulation, and six plasma markers of inflammation. Results: Fractal dimension was significantly higher in the sepsis and severe sepsis groups than the healthy control (1.78 ± 0.07 and 1.80 ± 0.05 respectively vs 1.74 ± 0.03) (p < 0.001), indicating a significant increase in mechanical clot strength and elasticity consistent with a hypercoagulable state. Conversely, fractal dimension was significantly lower in septic shock (1.66 ± 0.10, p < 0.001), indicating a significant reduction in mechanical clot strength and functionality consistent with a hypocoagulable state. This corresponded with a significant increase in the inflammatory response. Conclusions: This study confirms that clot microstructure is significantly altered through the various stages of sepsis. Of particular importance was the marked change in clot development between severe sepsis and septic shock, which has not been previously reported

Phase I Evaluation of Intravenous Ascorbic Acid in Combination with Gemcitabine and Erlotinib in Patients with Metastatic Pancreatic Cancer

Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy.14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week), using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier). There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of disease or treatment with gemcitabine or erlotinib. Applying RECIST 1.0 criteria, seven of the nine subjects had stable disease while the other two had progressive disease.These initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients. This, combined with the observed response to treatment, suggests the need for a phase II study of longer duration.Clinicaltrials.gov NCT00954525