SDF-1 enhances the expansion and maintenance of highly purified human hematopoietic progenitors

The stromal-derived factor-1 (SDF-1) chemokine and its putative receptor, CXCR4, have been implicated in hematopoiesis. Here we aim to characterize the effects of cytokine-induced CXCR4 expression and SDF-1 treatment on primitive human umbilical cord blood (CB) cells in vitro. Highly purified CD34+CD38-Lin-CXCR4- blood cells were capable of forming CD34+CXCR4+ cells during short-term liquid culture, but maintained distinct erythroid and myeloid progenitor composition, similar to the parent population prior to culture. In vitro, SDF-1 enhanced the expansion and differentiation of primitive CB cells in a manner that was dependent upon both the concentration of SDF-1 and the presence of specific cytokines. In the absence of cytokine addition, cultures seeded with CD34+CD38-Lin- cells demonstrated substantial cell death; however, the addition of SDF-1 alone preferentially increased progenitor cell frequency. Our study demonstrates that induction of CXCR4 expression does not alter the differentiative potential of human blood progenitors and suggests a role for SDF-1 as a growth factor required for human hematopoiesis.     

Atrial fibrillation: epidemiology, mechanisms and management

The incidence of AF, the most common sustained arrhythmia in clinical practice, increases with age and coronary artery disease, hypertension and valvular heart disease are common underlying substrates; however, occasionally, AF may occur without any underlying heart disease. The most widely accepted theory of its mechanism is Moe's multiple wavelet hypothesis, although recent studies are helping to shed light on other mechanisms, including the focal origin of AF in some patients. Most patients experience palpitations, but fatigue, dyspnoea, and dizziness may also occur. Therapy includes prevention of thromboembolism, control of rate, and restoration and maintenance of sinus rhythm. The risks and benefits of each treatment modality need to be assessed according to each patient's circumstances. Unlike other arrhythmias, there is still no highly successful therapy for treating AF. However, significant advances are being made using non-pharmacological approaches to either prevent or cure this troublesome arrhythmia.     

Hepatitis E virus antigen detection as an early diagnostic marker: Report from India

Hepatitis E virus (HEV) is implicated in many outbreaks of viral hepatitis in the Indian subcontinent. The conventional diagnosis of such outbreaks rests on the detection of anti‐HEV IgM antibodies. However, IgM antibodies develop after 4–5 days of infection. An early‐diagnostic marker is imperative for timely diagnosis of the outbreak and also initiation of control measures. This study aimed to determine the use of hepatitis E virus antigen detection as an early diagnostic marker in an outbreak in comparison to anti‐HEV IgM and RT‐PCR analyses. Forty samples were collected during a suspected outbreak of viral hepatitis due to HEV. A total of 36 samples were positive for one or more HEV markers. The positivity for anti‐HEV IgM, HEV antigen, and RT‐PCR was 91.6%, 69.4%, and 47.2% respectively. RT‐PCR and HEV antigen detection gave the highest positive results (100%) in the first 3 days of illness. Positive HEV PCR declined to 54% by Days 4–7, whereas HEV antigen and IgM detection were 88% and 100%, respectively. Sequencing of representative HEV samples indicated that the strains responsible for this outbreak belonged to genotype I, subtype 1a. HEV antigen was found to be an early diagnostic marker of acute infection. HEV antigen was detected in three additional cases in the early phase (1–3 days), and they had no detectable anti‐HEV IgM antibodies. These three samples were also positive for HEV RNA. After Day 7, anti‐HEV IgM was the main diagnostic indicator of infection. J. Med. Virol. 85:823–827, 2013. © 2013 Wiley Periodicals, Inc.     

Genomic DNA of MCF-7 breast cancer cells not an ideal choice as positive control for PCR amplification based detection of Mouse Mammary Tumor Virus-Like Sequences

The identification of the etiology of breast cancer is a crucial research issue for the development of an effective preventive and treatment strategies. Researchers are exploring the possible involvement of Mouse Mammary Tumor Virus (MMTV) in causing human breast cancer. Hence, it becomes very important to use a consistent positive control agent in PCR amplification based detection of MMTV-Like Sequence (MMTV-LS) in human breast cancer for accurate and reproducible results. This study was done to investigate the feasibility of using genomic DNA of MCF-7 breast cancer cells to detect MMTV-LS using PCR amplification based detection. MMTV env and SAG gene located at the 3′ long terminal repeat (LTR) sequences were targeted for the PCR based detection. No amplification was observed in case of the genomic DNA of MCF-7 breast cancer cells. However, the 2.7 kb DNA fragment comprising MMTV env and SAG LTR sequences yielded the products of desired size. From these results it can be concluded that Genomic DNA of MCF-7 cell is not a suitable choice as positive control for PCR or RT-PCR based detection of MMTV-LS. It is also suggested that plasmids containing the cloned genes or sequences of MMTV be used as positive control for detection of MMTV-LS.     

Role of Bile Acids in Liver Injury and Regeneration following Acetaminophen Overdose

Bile acids play a critical role in liver injury and regeneration, but their role in acetaminophen (APAP)–induced liver injury is not known. We tested the effect of bile acid modulation on APAP hepatotoxicity using C57BL/6 mice, which were fed a normal diet, a 2% cholestyramine (CSA)–containing diet for bile acid depletion, or a 0.2% cholic acid (CA)–containing diet for 1 week before treatment with 400 mg/kg APAP. CSA-mediated bile acid depletion resulted in significantly higher liver injury and delayed regeneration after APAP treatment. In contrast, 0.2% CA supplementation in the diet resulted in a moderate delay in progression of liver injury and significantly higher liver regeneration after APAP treatment. Either CSA-mediated bile acid depletion or CA supplementation did not affect hepatic CYP2E1 levels or glutathione depletion after APAP treatment. CSA-fed mice exhibited significantly higher activation of c-Jun N-terminal protein kinases and a significant decrease in intestinal fibroblast growth factor 15 mRNA after APAP treatment. In contrast, mice fed a 0.2% CA diet had significantly lower c-Jun N-terminal protein kinase activation and 12-fold higher fibroblast growth factor 15 mRNA in the intestines. Liver regeneration after APAP treatment was significantly faster in CA diet–fed mice after APAP administration secondary to rapid cyclin D1 induction. Taken together, these data indicate that bile acids play a critical role in both initiation and recovery of APAP-induced liver injury.Bile acids are versatile biological molecules that regulate energy homeostasis, activate nuclear receptors and cell signaling pathways, and control cell proliferation and inflammatory processes in the liver and gastrointestinal tract.^1,2 Bile acids maintain their own homeostasis by activating a complex signaling network involving hepatic and intestinal farnesoid X receptor (FXR), small heterodimer partner, and intestinal fibroblast growth factor (FGF) 15 (FGF19 in human) expression, culminating in inhibition of the primary bile acid–synthesizing enzyme, CYP7A1.^3–6 Although bile acids are potent signaling molecules at pathophysiological concentrations, they cause apoptosis, necrosis, and oxidative stress.^3,7–10 Bile acids have also been implicated in stimulation of liver regeneration.^11–14 Studies in recent years indicate that the bile acid–mediated gut-liver signaling axis may play a critical role in regulation of liver homeostasis.^6,15,16Acetaminophen (APAP) is the most commonly used analgesic and antipyretic agent.¹⁷ An overdose of APAP is the major cause of acute liver failure in the United States.^18,19 The mechanisms of APAP-induced liver injury and subsequent liver regeneration are the focus of intense investigation.^20–22 In an overdose situation, excess APAP is mainly metabolized by CYP2E1 to a reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI). In hepatocytes, conjugation of NAPQI to GSH is the key mechanism for detoxification of NAPQI. Once the GSH is depleted, NAPQI attacks cellular proteins, especially mitochondrial proteins, to form protein adducts. This triggers a cascade of intracellular signaling events involving c-Jun N-terminal protein kinase (JNK) activation and mitochondrial permeability transition, finally culminating in necrotic cell death.²⁰ Liver injury is followed by compensatory liver regeneration, which is a critical determinant of final outcome of liver injury.²³ Despite decades of research, how these intracellular events are affected by extracellular signaling is not known.The current study was designed to explore the role of bile acids in initiation of liver injury and stimulation of liver regeneration after APAP overdose. These studies are highly significant because the data reveal a novel role of bile acids in cellular protection and liver regeneration after APAP overdose, and these studies investigate the effect of resin-mediated bile acid depletion, a commonly used therapy, on APAP toxicity.     

Benchmarking Various Radiomic Toolkit Features While Applying the Image Biomarker Standardization Initiative toward Clinical Translation of Radiomic Analysis

Journal of Digital Imaging - The image biomarkers standardization initiative (IBSI) was formed to address the standardization of extraction of quantifiable imaging metrics. Despite its effort,...     

Timing of dental extractions in patients undergoing radiotherapy and the incidence of osteoradionecrosis: a systematic review and meta-analysis

This systematic review aimed to examine whether the incidence of osteonecrosis differed between patients who have dental extractions before or after radiotherapy (RT). The reported incidence of osteoradionecrosis (ORN) of the jaws following RT to the head and neck varies widely in the literature. Currently, for patients with head and neck cancer there are no universally accepted guidelines on the optimal timing of dental surgery relative to RT to minimise incident ORN. A literature review was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) criteria. A search of PubMed, EMBASE, Evidence-Based Medicine, and Web of Science databases targeted literature published up to and including 10 April 2020. Two independent reviewers assessed studies for eligibility against inclusion criteria. An assessment of bias was conducted for each of the included studies and relevant data extracted. A meta-analysis was undertaken using the statistical methods described. Twenty-four of 708 studies were included. They were heterogeneous and included a wide variation of RT methods, head and neck malignancies, and comorbidities. While some concluded that the incidence of ORN was dependent on the timing of dental extractions in relation to RT, with regard to the risk of its development, others reported additional factors such as age, comorbidities, extent of surgical resection, and dose and field of radiation, as more important predictors than timing. In many there was consistent lack of detail around the timing of dental procedures in relation to the delivery of RT. From 21 studies including 36,294 patients, of whom 14,389 had extractions before RT, the pooled incidence of ORN was 5.5% (95% CI: 2.1% to 10.1%). Significant heterogeneity was found in Cochran’s Q-test (p < 0.001) and Higgins I² = 98.0%. From 21 studies including 37,805 patients, of whom 6030 had extractions after RT, the pooled incidence of ORN was 5.3% (95% CI: 2.9% to 8.2%). Significant heterogeneity was found in Cochran’s Q-test (p < 0.001) and Higgins I² = 80.0%. There was no statistically significant difference between these two groups (random-effects model Q=0.12, p=0.73). Large, longitudinal studies with a priori-specified methods are needed to identify, recruit, and prospectively follow patients with head and neck cancer for the onset of ORN after dental surgery. This will allow clinical guidelines to be established to assist clinicians to plan treatment when extractions are indicated in patients undergoing RT to the head and neck.     

Oral and maxillofacial surgery patient satisfaction with telephone consultations during the COVID-19 pandemic

Due to the COVID-19 pandemic most oral and maxillofacial surgical (OMFS) units have moved to conducting patient consultations over the telephone. The aim of this study was to assess patients' satisfaction with telephone consultations during the COVID-19 pandemic. A retrospective survey was conducted of OMFS patients at our hospital who had telephone consultations between 1 April - 8 June 2020. The survey was conducted by independent interviewers and used the Generic Medical Interview Satisfaction Scale (G-MISS) along with a previously published additional questionnaire. Variables recorded included age, gender, theme of consultation, grade of clinician, and type of consultation. Statistical analysis was performed to assess for any differences between patient groups. The records of 150 consecutive patients were reviewed and 135 met inclusion criteria. A total of 109 patients completed the survey giving a response rate of 80.74%. The total G-MISS score for satisfaction was high, which indicates a high level of satisfaction among all patients. We found no statistical difference in satisfaction when comparing patients in terms of gender, age, theme of consultation, or level of clinician. A significant difference was found in compliance levels between review and new patients, with review patients demonstrating higher compliance levels (p=0.004). Overall, 83.48% of patients said they would be willing to have a telephone consultation in future. The majority of patients in this study reported high levels of satisfaction with telephone consultations. New patients reported lower levels of compliance which may suggest this type of consultation is less suited to telephone consultation.