Spontaneous Incidence Research Articles

Reproductive factors and risk of spontaneous abortion

One of the causes of bleeding and infection in pregnant women is abortion-a failure reproduction. Spontaneous abortion is a pregnancy complication that can affect women both physically and psychologically. This research was purposed to find out the spontaneous abortion incidence, the relation of mother’s age to the spontaneous abortion incidence by controlling the others risk factors such as the interval of the pregnancy, parity, and the usage of contraception. Type to the research is a case-control study where the number of subjects is 174 of pregnant women who have a spontaneous abortion as the case and who have no spontaneous abortion as the controlled group. The univariable used distribution of frequency, the analysis of bivariable used chi-square test, and the analysis of multivariable used multiple logistic regression analysis. The proportion of case group was The largest sample proportion in the case group for the age variable was at the age of 20-35 years (48.3%), pregnancy interval ≥2 years (56.9%), parity gave birth more than 4 times (62.1%), and use contraception (56.9%). Meanwhile, the control group for the variable age was at the age of 20-35 years (78.4%), pregnancy interval ≥2 years (79.3%), parity between 2-3 births (57.8%), and use contraception (73.6%). All variables were associated with the incidence of spontaneous abortion as follow age of mother 35 years old (p-value 0.000; OR 3.61; 95% CI 1.17-11.07), pregnancy interval (p-value 0.002; OR 2.90; 95% CI 1.38-6.10), parity (p-value 0.013; OR 2.24; 95% CI 1.12-4.51), use of contraception (p-value 0.000; OR 3.43; 95% CI 1.59-7.34). The most dominant factor was mother age <20 years old (OR: 3.82; 95% CI 1.64-8.94). Mothers aged <20 years are at high risk for spontaneous abortion.

Lethal Provocation: The Constantine Murders and the Politics of French Algeria by Joshua Cole

Reviewed by: Lethal Provocation: The Constantine Murders and the Politics of French Algeria by Joshua Cole Benjamin Sparks Cole, Joshua. Lethal Provocation: The Constantine Murders and the Politics of French Algeria. Cornell UP, 2019. ISBN 978-1-5017-3941-5. Pp. 317. Relations between the Jewish and Muslim populations in Constantine in eastern Algeria during the interwar period reached a climax in August 1934 with the riots and murder of twenty-five Jews and three Algerian Muslims. The tension between these two parties traces its origins largely to issues of citizenship and the Crémieux decree of 1870, which allotted a majority of the Algerian Jewish population full French [End Page 233] citizenship. However, the Muslim community was not granted the same access and remained under second-class indigenous status outlined in the Code de l'Indigénat. With this citizenship, the Jews were allowed to vote while only representing 12% of the population. Meanwhile, they represented 25% of the electorate. The distinction between Europeans, Muslims, and Jews shaped the politics of colonial Algeria, and the strain on political relations among these groups provides some of the background details that lead to the riots and murders of 1934. Mohammed Salah Bendjelloul, an Algerian Muslim and proponent for electoral reform, contributed to the strife in the French political system and became a leading spokesperson for his community and political alliance, the Fédération des élus musulmans de Constantine. The official report of the 1934 events, never released to the public but accessible through the archives today, blames the violence and riots on religious fanaticism. Initial speculation blamed this fanaticism on Bendjelloul's followers. Joshua Cole, however, argues that our understanding of the events requires a reevaluation of the riots and murders as acts of provocation by a small group and not unrelated spontaneous incidents of religious fanaticism. To address this revision, Cole approaches this history by arguing that Mohamed El Maadi, a soldier in the French army, was not only a local conspirator but also an infamous extremist who, as part of a larger unknown organization, planned, provoked, and led the murders of at least twenty of the Jewish victims on 5 August 1934. El Maadi's participation, however, was not included in official reports and investigations, leading to an apparent cover-up due to possible links with four separate levels of government authority in Constantine. Shortly after the riots, El Maadi departed the region on a six-month leave due to previous injuries sustained in 1927, suggesting, as Cole does, that his superiors wanted him far from the investigation. A later unrelated document about a political murder in 1938 from the same organization that led the investigation in Constantine, the police mobile, indicates that the police believed El Maadi to be the leading force of the violence on 5 August. Cole provides a history of El Maadi's life after the 1934 events to indicate his anti-Semitic inclinations, including his role in the Vichy government and later involvement in the German SS, to validate the hypothesis that El Maadi had been the leading figure for the murder of the Jews that day. Cole's history of the murders in Constantine provides an intriguing reading of a murder mystery and its cover-up, interconnected in the sociopolitical history of colonial Algeria. Benjamin Sparks University of Memphis (TN) Copyright © 2020 American Association of Teachers of French

Numerical investigation of coal self-heating in longwall goaf considering airflow leakage from mining induced crack

Self-heating of coal is a long-standing hazard and pollution source in longwall goaf and abnormal air leakage into goaf is a key yet complex drive to the hazard. To investigate such a problem with more insights, a numerical model without considering coal moisture is established based on a Shendong longwall. Abnormal air leakage into goaf mainly sources from the edge cracks resulting in presence of high level oxygen (8 %∼13 %) in start-off area of the longwall. Two heating liable regimes were identified: one is behind longwall face and another one locates in the start-off zone. Heating in the start-off zone develops more quickly than that in heating regime one. On day 25 the maximum temperature of regime two can rise to 500K while it can only increase to approximately 340K in regime one. The heating spot behind longwall face tends to be self-suppressed with longwall advancing while the heating in the start-off zone can develop to a spontaneous combustion incident due to constant airflow leakage from the mining induced cracks. A wide range of inertisation plans including different locations, strategies, and flowrates of nitrogen injection were conducted. An optimum inertisation plan is to proactively inject inert gas with a low flowrate (e.g. 122m3/h) from a seal along the start-off line. A high flowrate of nitrogen stream is preferable to suppress an on-going heating and the reactive inertisation should be maintained for a long run otherwise the heating is very likely to re-develop.

Analysis of β-catenin gene mutations and gene expression in liver tumours of C57BL/10J mice produced by chronic administration of sodium phenobarbital

In this study liver tumours produced in male and female mice of the low spontaneous liver tumour incidence C57BL/10J strain treated for 99 weeks with 1000 ppm in the diet with the model constitutive androstane receptor (CAR) activator sodium phenobarbital (NaPB) were analysed for β-catenin mutations by Western immunoblotting and DNA/RNA analysis. Some gene array analysis was also performed to identify genes involved in CAR activation and in β-catenin and Hras gene mutations. Analysis of 8 male and 2 female NaPB-induced liver tumour samples (comprising 2 adenomas, 6 carcinomas and 2 samples containing separate adenomas and carcinomas) revealed truncated β-catenin forms in just 4 male liver tumour samples, with the presence of the truncated β-catenin forms being confirmed by β-catenin exon 1–3 mutation analysis. Microarray gene expression analysis was performed with three of the NaPB-induced male mouse liver tumour samples where β-catenin mutations had not been identified by Western immunoblotting and DNA/RNA analysis and with three liver samples from both NaPB-induced non-tumour tissue and control animals. Treatment with NaPB resulted in induction of Cyp2b subfamily gene expression in both NaPB-induced mouse liver tumours and in NaPB-treated non-tumour tissue. In addition, the gene expression analysis demonstrated that the β-catenin and Hras pathways were not modified in NaPB-induced mouse liver tumours not exhibiting truncated β-catenin forms. Overall, while chronic administration of the model CAR activator NaPB results in both hepatocellular adenoma and carcinoma in the low spontaneous liver tumour incidence C57BL/10J mouse strain, only 40 % of the liver tumours evaluated in this study had β-catenin mutations. These results are in agreement with previous studies with the CAR activator oxazepam and demonstrate that mouse liver tumours induced by nongenotoxic CAR activators in the absence of initiation with a genotoxic agent are due to a number of mechanisms, including those largely independent of either the Wnt/β-catenin signalling pathway or Hras oncogene mutations.

Acid suppression therapy and its association with spontaneous bacterial peritonitis incidence: A systemic review and meta-analysis.

It is well known that the use of proton pump inhibitor (PPI) is widespread in patients with liver cirrhosis. PPI counteracts H2 receptor inhibitor (H2 RA) with its strong acid suppression effect. However, there is always a concern that PPI use may increase spontaneous bacteria peritonitis (SBP) development in cirrhotic patients. We aimed to investigate the association between acid suppression therapy (i.e. PPI or H2 RA) and SBP through meta-analysis. We searched PubMed, Medline, Web of Science, Cochrane library, and Embase for relevant studies published up to April 2019. Pooled OR and 95% CI were calculated by a random-effects model. Funnel plots and Egger's tests were performed for the evaluation of publication bias. Non-parametric "trim-and-fill" tests were conducted for sensitivity analysis. A total of 20 original articles including 9566 cirrhotic patients were analyzed. The overall meta-analysis highlighted that PPI use was associated with the risk of SBP (pooled OR 1.77, 95% CI 1.49-2.11). The conclusion was irrespective of study methods, whereas the result was inconsistent only in South America. However, the conclusion might not be stable enough and should be extrapolated with caution. Unlike PPI, we found H2 RA was not associated with SBP (pooled OR 1.06, 95% CI 0.75-1.48). In conclusion, PPI use, but not H2 RA, will increase the incidence of SBP in cirrhotic patients. In addition, H2 RA might be beneficial for patients who require long-term acid suppression therapy.

Spontaneous subarachnoid haemorrhage incidence among hospitalised patients in Edirne, Turkey.

To the best of our knowledge, no data has been published about the spontaneous subarachnoid haemorrhage (sSAH) incidence in Turkey. We aimed to report the estimation of sSAH incidence in Edirne Province, in Turkey for the first time, using the data acquired from a single medical centre which has the biggest and the most comprehensive emergency department in Edirne and to where a great majority of patients are referred. We investigated all the accessible sSAH patients' data obtained from computer-based automation systems and all the written documents in the neurosurgery and the emergency departments. Patients included in the study were diagnosed with sSAH between the dates of January 2007 and December 2011 and were resident in Edirne. We used this data to calculate the crude and age-adjusted incidence rates of sSAH for every decade. One hundred fifty-four patients have been diagnosed with sSAH during a 5-year period. Among them, 72 were men (47.8%) and 82 (53.2%) were women. The mean age of the patients was 60.8years and age range was 23-85years. The overall annual adjusted incidence rate for sSAH was 10.3 per 100,000 person-years (95% confidence interval = 10.2-10.3). Annual adjusted incidence rate was 10 per 100,000 person-years (95% confidence interval = 10-10.1) for men. For women, it was 10.4 per 100,000 person-years (95% confidence interval = 10.4-10.5). For both sexes, after the 6th decade, the annual incidence rate of sSAH was higher than 10 per 100,000, reaching over 20 per 100,000 person-years after the 7th decade. The overall crude incidence rate for sSAH was 10.3 per 100,000 person-years. For men, the crude incidence rate was 9.4 per 100,000 person-years and for women, it was 11.2 per 100,000 person-years. This study showing the first sSAH incidence estimation in Edirne might also be accepted as an estimation of overall epidemiological sSAH aspect in Turkey. Future investigations should be realised in different parts of Turkey to enlighten the epidemiological state of affairs and the course of sSAH in Turkey.

Resting Heart Rate Variability Predicts Vulnerability to Pharmacologically-Induced Ventricular Arrhythmias in Male Rats.

The electrical stability of the myocardium is dependent on the dynamic balance between sympathetic and parasympathetic influences on the heart, which is reflected by heart rate variability (HRV). Reduced HRV is a proposed predictor of sudden death caused by ventricular tachyarrhythmias in cardiac patients. However, the link between individual differences in HRV and ventricular tachyarrhythmic risk in populations without known pre-existing cardiac conditions is less well explored. In this study we investigated the extent to which individual differences in resting state HRV predict susceptibility to spontaneous and pharmacologically-induced ventricular arrhythmias in healthy rats. Radiotelemetric transmitters were implanted in 42 adult male Wild-type Groningen rats. ECG signals were recorded during 24-h resting conditions and under β-adrenoceptor pharmacological stimulation with isoproterenol and analyzed by means of time- and frequency-domain indexes of HRV. No significant association was found between individual differences in resting measures of HRV and spontaneous incidence of ventricular arrhythmias. However, lower resting values of HRV predicted a higher number of ventricular ectopic beats following β-adrenergic pharmacological stimulation with isoproterenol (0.02 mg/kg). Moreover, after isoproterenol administration, one rat with low resting HRV developed sustained ventricular tachycardia that led to death. The present results might be indicative of the potential utility of HRV measures of resting cardiac autonomic function for the prediction of ventricular arrhythmias, particularly during conditions of strong sympathetic activation, in populations without known cardiac disease.

Breast cancer occurrence after low dose radiotherapy of non-malignant disorders of the shoulder

Stochastic long-term damages at relatively low doses have the potential for cancer induction. For the first time we investigated the occurrence of breast cancer in female patients after radiotherapy of non-malignant disorders of the shoulder and made a comparison with the estimated spontaneous incidence of mammary carcinoma for this cohort. In a geographically defined district with a population of approximately 100.000 inhabitants, comprehensive data of radiological diagnostics and radiotherapy were registered nearly completely for 41 years; data included mammography and radiotherapy of breast cancer patients as well as of non-malignant disorders. Within this population a collective of 158 women with radiotherapy of the shoulder was investigated. Radiotherapy was performed with cobalt-60 photons (Gammatron) with an average cumulative-dose of 6 Gy. The average follow-up time was 21.3 years. Patients were 55 years old (median) when radiotherapy of the shoulder was performed. Seven patients (4.4%) developed breast cancer after a median of 21 years. According to the incidence statistics, 9.4 +/− 1.8 (95%CI) cases (5.9%) would be expected. In regard to the irradiated shoulder neither the ipsilateral nor the contralateral breasts showed increased rates of breast cancer. An induction of additional breast cancer caused by radiation of non-malignant disorders of the shoulder wasn’t detected in the investigated cohort.

Computational Investigation of Amyloid Peptide Channels in Alzheimer’s Disease

Aβ accumulation has been discovered to form large, relatively cation-permeable channels in the plasma membrane of a neuron. These channel formations in the membranes of a neuron could cause cell depolarisation, sodium and potassium dysregulation, depletion of neural energy stores and other types of cellular dysfunction. This study shows that the build-up of amyloid beta (Aβ) depositions during the onset of Alzheimer’s disease has profound effects on the activity of the local community of neurons in the central nervous system. These effects can include enhanced neural activity, spontaneous epileptiform activity and incidence of epileptic seizures. From the results in this area, it can be seen that the neurodegeneration observed in Alzheimer’s disease has been associated with the increase of toxicity of Aβ depositions. In this research paper, we examined this hypothesis in light of a computational model of a neuron.

Heterozygous Tsc2 (Tsc2+/-) mouse model to study induced renal cancer in response to ionizing radiation at low doses.

Kidneys are one of the main dose-limiting organs in radiotherapeutic procedures of lower abdomen. Likewise, the threat of exposure of radiosensitive organs such as kidneys in warfare or radiation accidents among military personal or due to terrorist activities in general public is of increasing concern. These events warrant the need for appropriate animal models to study the acute and chronic effects of low- and high-dose rate radiation exposures. In this study, for the first time, we validated Tsc2+/- mouse model to study whether radiation accelerates carcinogenesis in kidneys. Tsc2+/- mice at increasing age groups at 8 and 10 months were exposed to repeated doses of gamma radiation (0.4 Gy × 5) and assessed for aggravated kidney tumor formation at 2 months post-irradiation. Animals from irradiated group showed a significant increase in numbers of bilateral, multifocal tumors compared with mock-irradiated animals. Intra-glomerular reactive oxygen species (ROS) levels measured by dihydroethidium florescence showed significant increases in ROS production in irradiated Tsc2+/- mice compared with non-irradiated animals. Similarly, selective hematological parameters and glomerular filtration rate were further reduced significantly in irradiated Tsc2+/- mice. Tsc2 protein, tuberin in irradiated mice, however, remains at the same reduced levels as that of the mock-irradiated heterozygous Tsc2 mice. The results indicate that radiation alters kidney homeostatic function and influences high spontaneous incidence of renal cell carcinoma in this rodent model. Repurposing of Tsc2+/- mice model will, therefore, provide a unique opportunity to study acute and delayed effects of radiation in the development of kidney cancers.

Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance and seroconversion in hepatitis B e antigen‐negative chronic infection patients: A population‐based prospective cohort

Seroclearance of hepatitis B surface antigen (HBsAg) has been widely studied; however, seroconversion of HBsAg and characteristics of viral load among hepatitis B e antigen (HBeAg)-negative chronic infection patients after HBsAg lost is not clear. We performed a large-scale study in a HBeAg-negative chronic infection cohort to evaluate spontaneous HBsAg seroclearance incidence from October 2012 to April 2017 in Jiangsu province, China. We also elucidated the characteristics of HBsAg seroconversion and hepatitis B virus (HBV) DNA detectability among patients who cleared HBsAg. A total of 2997 HBeAg-negative chronic infection patients (mean age 52.3±12.9years at baseline) were included. With 10519 person-years of follow-up, 348 patients successfully spontaneously cleared HBsAg, with an incidence rate of 3.31 per 100 person-years. Patients with HBV DNA detectable ~1999IU/mL at baseline had a lower probability of HBsAg seroclearance relative to those with undetectable HBV DNA, with a hazard ratio of 0.31 (95% CI=0.23, 0.41). HBsAg seroconversion occurred in 37.3% of those patients who cleared HBsAg. The geometric mean of anti-HBs among those with HBsAg conversion was 79.4mIU/mL. Female had a higher HBsAg seroconversion rate (P=0.011). Among those with HBsAg seroclearance, 11.2% still had HBV DNA levels of higher than 100IU/mL. Patients with higher HBV DNA at baseline had a higher risk of detectable HBV DNA levels even after HBsAg seroclearance (P<0.001). This study reveals HBsAg seroconversion rates and HBV DNA undetectability epidemiological characteristics of patients with HBsAg seroclearance and suggests that monitoring HBV DNA is needed when managing HBeAg-negative chronic patients, even after clearing HBsAg.

Abstract 394: The Role Of Camkii-dependent Late Sodium Current In Ischemia/reperfusion-associated Arrhythmogenesis

Ischemic heart disease is the leading cause of death in the world. Importantly, CaMKII activity is upregulated during ischemia/reperfusion (I/R). However, the mechanisms by which CaMKII induces arrhythmias remains incompletely understood. We tested the hypothesis that CaMKII-dependent upregulation of the late Na+ current (INa,L) via direct phosphorylation of Nav1.5 at Ser571 is responsible for increased arrhythmia susceptibility during I/R. The role of CaMKII-dependent regulation of INa,L was explored using mice harboring Nav channel variants Nav1.5-Ser571E (S571E, phosphomimetic) and Nav1.5-Ser571A (S571A, phosphorylation incompetent). Isolated, perfused WT, S571E and S571A hearts were subjected to global ischemia (15 min) followed by reperfusion (15 min). Immunoblots demonstrated a significant increase in phosphorylated Nav1.5 at Ser571 in WT hearts during I/R compared to baseline (2.2±0.3 vs 1.0±0.3, respectively; P&lt;0.05, n=5). Optical mapping using the voltage-sensitive dye di-4-ANEPPs (4 μM) revealed a significant increase in action potential duration in WT and S571E mice compared to S571A during I/R (WT: 55.2±0.6 ms*, S571E: 70.0±2.3 ms*, S571A: 46.0±2.9 ms; *P&lt;0.05 vs. S571A, n=5/genotype). Furthermore, spontaneous arrhythmia incidence was increased in WT and S571E hearts (WT: 0.60±0.06 events/min*, S571E: 0.81±0.14 events/min*, S571A : 0.23±0.03 events/min; *P&lt;0.05 vs. S571A, n=5/genotype). Interestingly, arrhythmia inducibility using an S1-S2 protocol was also increased in WT and S571E hearts (WT: 80%*, S571E: 100%*, S571A: 0%; *P&lt;0.05 vs. S571A, n=5/genotype). The Na+ channel blocker mexiletine (10 μM) normalized APD and decreased arrhythmia inducibility in WT hearts during I/R (0% arrhythmia incidence in WT hearts treated with mexiletine). These data indicate a central role for CaMKII-dependent phosphorylation of Nav1.5 and augmentation of INa,L in the development of arrhythmogenesis during I/R.

PDCB does not promote CNS autoimmunity in the context of genetic susceptibility but worsens its outcome

BackgroundPara-dichlorobenzene (PDCB) is an aromatic hydrocarbon contained in mothballs that is potentially neurotoxic. A potential pathogenic role of PDCB in MS pathogenesis has been suggested. MethodsTo determine the ability of chronic PDCB ingestion to induce CNS autoimmunity in a genetically susceptible mammalian species, naive myelin oligodendrocyte glycoprotein peptide (MOGp)35–55 T cell receptor (TCR) transgenic mice (2D2) on the C57Bl/6 background were orally gavaged once daily with corn oil control, 125 mg/kg PDCB, or 250 mg/kg PDCB for 45 days. The incidence of spontaneous EAE is increased in this mouse strain. ResultsBoth PDCB treatment groups showed the same spontaneous incidence of EAE, an earlier disease onset, and a slight decrease in survival for 125 mg/kg PDCB mice compared to control mice. We were unable to detect any PDCB, or its metabolites 2,5-dichlorophenol, 2,5-dicholormethylsulfide, and 2,5-dichloromethylsulfone in the brain and spinal cord of control mice. In contrast, PDCB was readily detectable in both compartments in mice who received PDCB via oral gavage, with concentrations being significantly higher in the brain (p < 0.01). Levels of the metabolites 2,5-dichlorophenol and 2,5-dichloromethylsulfone were also significantly higher in brains compared to spinal cords. ConclusionOur study refutes the hypothesis that PDCB or its metabolites trigger spontaneous T cell-mediated CNS autoimmunity in the setting of genetic susceptibility. A slight increase in mortality with PDCB exposure may be due systemic toxicity of hydrocarbons.

Dose-dependent impact of proton pump inhibitors on the clinical course of spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis is a severe complication in patients with cirrhosis leading to acute kidney injury, hepatic encephalopathy and a high mortality. In this study, we aimed to investigate the impact of proton pump inhibitors and the potential relevance of the taken dosage on the incidence and clinical course of spontaneous bacterial peritonitis. Overall, 613 consecutive patients with decompensated cirrhosis were included. All patients were carefully evaluated for proton pump inhibitors intake including the applied dosage and were further followed up for spontaneous bacterial peritonitis development as well as for the incidence of clinical complications like hepatic encephalopathy, acute kidney injury and mortality. Cumulative spontaneous bacterial peritonitis incidence did neither differ between the proton pump inhibitors and the no-proton pump inhibitors group nor between those taking the high (>40mg/d) and the low (10-40mg/d) proton pump inhibitors' dose. However, proton pump inhibitors' intake was associated with an impaired clinical course of spontaneous bacterial peritonitis reflected by a higher likelihood for acute kidney injury (71% vs 43%; P=.002), severe hepatic encephalopathy (15% vs 0%; P=.04) and an increased mortality (24% vs 0%; P=.008) within 28days after spontaneous bacterial peritonitis diagnosis. In particular, patients with proton pump inhibitors dosages >40mg/d had an increased short-term risk for acute kidney injury (adjusted hazard ratio: 1.86; P=.009) and mortality (adjusted hazard ratio: 2.05; P=.02). In contrast, there was no effect of proton pump inhibitors on acute kidney injury, hepatic encephalopathy and mortality in patients without spontaneous bacterial peritonitis irrespective of the applied proton pump inhibitors dosage. High dosages of proton pump inhibitors are associated with an adverse outcome in patients with spontaneous bacterial peritonitis. Thus, indication for high-dosage proton pump inhibitors therapy should be evaluated carefully in these patients.

The inducement of coal spontaneous combustion disaster and control technology in a wide range of coal mine closed area

Based on the theory of coal and oxygen interaction mechanism and combined with the actual situation of a coal spontaneous combustion incident at Wangtaipu coal mine, the occurrence conditions, process, and the degree of risk of spontaneous combustion in the closed area are analyzed in detail. The main reasons for the coal spontaneous combustion in the closed area were obtained by the extraction and analysis of the multiinformation. The fractures on the seal walls were analyzed. Their distribution characteristics and air leakage were investigated. According to the distribution concentration of CO and O2 and their variety law in the entire closed area, the range of the fire zone was delineated. After that, multiple technical measures were implemented, such as fracture plugging, even pressure for air control, and absorbing and cooling temperature by injecting nitrogen. The concentration changes of CO, O2, and CO2 in the closed area are controlled, and the temperature and pressure difference are obviously reduced. The use of multiple information to analysis the degree of spontaneous combustion in the closed area and the multiple fire extinguishing technology has been demonstrated successful in the practical application. The proposed techniques can be applied to other similar conditions for prevention and control of hazards imitated from coal spontaneous combustion.

High Background Incidence of Spontaneous Subcapsular Adrenal Gland Hyperplasia of Tg.rasH2 Mice Used in 26-week Carcinogenicity Studies.

The Tg.rasH2 model was accepted by regulatory agencies worldwide for 26-week carcinogenicity assays as an alternative to the standard 2-year assays in conventional mice in 2003. Several references documenting spontaneous nonneoplastic findings and incidences of spontaneous tumors in the Tg.rasH2 mice have been published. The purpose of this publication is to add adrenal gland subcapsular hyperplasia to the database pertaining to spontaneous lesions noted in Tg.rasH2 mice, review physiology related to this finding, and discuss its significance. The incidence of spontaneous subcapsular adrenal gland hyperplasia was determined in control Tg.rasH2 mice from nine 26-week carcinogenicity studies carried out within the last 5 years at two contract research organizations. Incidence of this finding ranged from 56% to 79% in males and 88% to 100% in females, with an incidence average of 62% in males and 93% in females. Adrenal gland subcapsular hyperplasia is a common finding in male and female Tg.rasH2 mice that did not progress to neoplasia in Tg.rasH2 mice. In general, it tends to be more frequent and severe in females in comparison to males.

Chemopreventive and Antitumor Efficacy of Curcumin in a Spontaneously Developing Hen Ovarian Cancer Model.

We investigated the effect of daily dietary curcumin intake on the development and progression of spontaneous ovarian cancer in a galline (hen) model, as the chicken is the only nonhuman animal in which ovarian cancer spontaneously develops with a high prevalence. At the end of 12 months, ovarian cancer had spontaneously developed in 39% (35/90) of control hens not fed curcumin (n = 90). In comparison, it spontaneously developed in 27% (24/90) and 17% (15/90) of hens given curcumin at 25.8 (n = 90) and 53.0 mg/day (n = 90), respectively (P = 0.004). This represented significant dose-dependent reductions in overall ovarian cancer incidence in the 25.8 and 53.0 mg/day curcumin-fed groups (31% and 57%, respectively). Daily curcumin intake also reduced ovarian tumor sizes (P = 0.04) and number of tumors (P = 0.006). Evaluation of the molecular mechanisms underlying the chemopreventive and antitumor effects of curcumin revealed that NF-κB and STAT3 signaling pathways were significantly inhibited but that the nuclear factor erythroid 2/heme oxygenase 1 antioxidant pathway was induced by curcumin intake in a dose-dependent manner in ovarian tissues (P < 0.05). Sequencing of the Ras family genes (KRAS, NRAS, and HRAS) revealed less frequent KRAS and HRAS mutations in ovarian tumors in the curcumin-fed animals. In conclusion, our results demonstrated for the first time that daily curcumin intake leads to a significant and dose-dependent reduction in spontaneous ovarian cancer incidence and tumor growth, indicating a tremendous role for curcumin as a chemopreventive strategy for ovarian cancer. Cancer Prev Res; 11(1); 59-67. ©2017 AACR.

Chemical and mineralogical characterization of highly and less reactive coal from Northern Natal and Venda-Pafuri coalfields in South Africa

Spontaneous combustion of coal is a major hazard associated with the coal mining industry over centuries. It also a major cause of underground fires in South African collieries and in opencast operations, spoil heaps and stockpiles. Spontaneous combustion incidents are manifested in all major aspects of coal mining namely, underground mining, surface mining, including during sea-borne transportation, storage and waste disposal. Previous studies indicate that there are various factors (both intrinsic and extrinsic) that influence the spontaneous combustion of coals.This paper characterizes highly reactive coal from the Vryheid coalfields and less reactive coal from at Venda-Pafuri coalfield, to identify and delineate some intrinsic coal parameters that are considered to be most critical in terms of heat ‘generation’ and relationships between the two coals types by tracing their similarities and differences in their spontaneous combustion parameters. Various tests were carried out to characterize these coals in terms of their intrinsic properties, namely: ultimate, proximate, petrographic analysis and Glasser spontaneous tests.The ultimate and proximate analysis showed that spontaneous coal has high contents of carbon, oxygen, and volatile matter as compared to non-spontaneous coal, making it more susceptible to spontaneous combustion. Non-spontaneous coal has higher ash content than the spontaneous coal. Furthermore, the petrographic analysis showed that spontaneous coal has high total reactivity compared to the non-spontaneous coal. Results from Glasser spontaneous test indicate that spontaneous coal absorbs more oxygen than non-spontaneous coal, which explains why spontaneous coal is more susceptible to spontaneous combustion. High reactive coal has low values of critical self-heating temperature (CSHT), indicating that this coal has potential of spontaneous ignition.

Triptolide-Assisted Phosphorylation of p53 Suppresses Inflammation-Induced NF-κB Survival Pathways in Cancer Cells.

Chronic inflammation plays important roles in cancer initiation and progression. Resolving chronic inflammation or blocking inflammatory signal transduction may prevent cancer development. Here, we report that the combined low-dose use of two anti-inflammatory drugs, aspirin and triptolide, reduces spontaneous lung cancer incidence from 70% to 10% in a mouse model. Subsequent studies reveal that such treatment has little effect on resolving chronic inflammatory conditions in the lung, but it significantly blocks the NF-κB-mediated expression of proliferation and survival genes in cancer cells. Furthermore, triptolide and aspirin induce distinct mechanisms to potentiate each other to block NF-κB nuclear localization stimulated by inflammatory cytokines. While aspirin directly inhibits IκB kinases (IKKs) to phosphorylate IκBα for NF-κB activation, triptolide does not directly target IKKs or other factors that mediate IKK activation. Instead, it requires p53 to inhibit IκBα phosphorylation and degradation. Triptolide binds to and activates p38α and extracellular signal-regulated kinase 1/2 (ERK1/2), which phosphorylate and stabilize p53. Subsequently, p53 competes with IκBα for substrate binding to IKKβ and thereby blocks IκBα phosphorylation and NF-κB nuclear translocation. Inhibition of p38α and ERK1/2 or p53 mutations could abolish the inhibitory effects of triptolide on NF-κB. Our study defines a new p53-dependent mechanism for blocking NF-κB survival pathways in cancer cells.

Eight millimetre covered TIPS does not compromise shunt function but reduces hepatic encephalopathy in preventing variceal rebleeding

Currently, there are no recommendations in guidelines concerning the preferred diameter of stents for transjugular intrahepatic portosystemic shunt (TIPS), owing to the lack of adequate evidence. We therefore compared 8mm stents with 10mm stents, to evaluate whether 8mm stents would achieve similar shunt function, with less hepatic encephalopathy (HE) and better liver function. Cirrhotic patients were randomly assigned to receive TIPS with an 8mm or 10mm covered stent to prevent variceal rebleeding. The primary endpoint was shunt dysfunction. All-cause rebleeding, orthotopic liver transplantation (OLT)-free survival, their composite endpoint, overt HE (overall and spontaneous) and liver function were designated as the secondary endpoints. From July 2012 to January 2014, 64 and 63 patients were allocated to the 8mm and 10mm groups, respectively. During a median follow-up of 27months in both arms, dysfunction rates (16% vs. 16% at two years, p=0.62), two-year rebleeding (16% vs. 17%, p=0.65), OLT-free survival (95% vs. 86%, p=0.37), and the composite endpoint (p=0.62) were not statistically different between the groups. Despite a marginal decrease in overall overt HE, there were significantly fewer spontaneous overt HE incidents in the 8mm group within two years (27% vs. 43%, p=0.03), with a risk reduction of 47%. Notably, patients receiving 8mm stents also developed less hepatic impairment. TIPS with 8mm covered stents showed similar shunt function to TIPS with 10mm stents, but halved the risk of spontaneous overt HE and reduced hepatic impairment. Therefore, 8mm TIPS stents should be preferred for the prevention of variceal rebleeding in cirrhotic patients. Lay summary: The optimal diameter for transjugular intrahepatic portosystemic shunt (TIPS) remained uncertain. This study showed that TIPS with 8mm covered stents did not compromise shunt patency, or influence the efficacy of variceal rebleeding prevention compared to TIPS with 10mm stents, but reduced the risk of spontaneous overt hepatic encephalopathy and the incidence of severe encephalopathy. Moreover, liver function reserve was also better in the 8mm stents group, suggesting that 8mm TIPS stents should be preferred for the prevention of variceal rebleeding in cirrhotic patients.