Previous studies from our group and others have shown that cyclooxygenase-2 (COX-2) has an essential role in radiation-induced non-targeted responses and genomic instability in vivo. However, the ...signalling pathways involved in such effects remain unclear.
A 1 cm(2) area (1 cm × 1 cm) in the lower abdominal region of gpt delta transgenic mice was irradiated with 5 Gy of 300 keV X-rays. Nimesulide, a selective COX-2 inhibitor, was given to mice for five consecutive days before irradiation. Changes in transforming growth factor-beta (TGF-β) and TGF-β receptor type-1 (TGFBR1) mediated signalling pathways, in the out of radiation field lung and liver tissues were examined.
While the plasma level of cytokines remained unchanged, the expression of TGF-β and its receptors was elevated in non-targeted lung tissues after partial body irradiation. In contrast to the predominant expression of TGF-β in stromal and alveolar cells, but not in bronchial epithelial cells, TGF-β receptors, especially TGFBR1 were significantly elevated in non-targeted bronchial epithelial cells, which is consistent with the induction of COX-2. The different expression levels of TGFBR1 between liver and lung resulted in a tissue specific induction of COX-2 in these two non-targeted tissues. Multiple TGF-β induced signalling pathways were activated in the non-targeted lung tissues.
The TGFβ-TGFBR1-COX-2 Signalling Pathway has a critical role in radiation-induced non-targeted response in vivo.
Minimally legally invasive dentistry Lam, R
Australian dental journal,
December 2014, 2014-Dec, 2014-12-00, 20141201, Letnik:
59, Številka:
4
Journal Article
Recenzirano
One disadvantage of the rapid advances in modern dentistry is that treatment options have never been more varied or confusing. Compounded by a more educated population greatly assisted by online ...information in an increasingly litigious society, a major concern in recent times is increased litigation against health practitioners. The manner in which courts handle disputes is ambiguous and what is considered fair or just may not be reflected in the judicial process. Although legal decisions in Australia follow a doctrine of precedent, the law is not static and is often reflected by community sentiment. In medical litigation, this has seen the rejection of the Bolam principle with a preference towards greater patient rights. Recent court decisions may change the practice of dentistry and it is important that the clinician is not caught unaware. The aim of this article is to discuss legal issues that are pertinent to the practice of modern dentistry through an analysis of legal cases that have shaped health law. Through these discussions, the importance of continuing professional development, professional association and informed consent will be realized as a means to limit the legal complications of dental practice.
The immunoreceptor NKG2D originally identified in natural killer (NK) cells recognizes ligands that are upregulated on tumor cells. Expression of NKG2D ligands (NKG2DL) is induced by the DNA damage ...response (DDR), which is often activated constitutively in cancer cells, revealing them to NK cells as a mechanism of immunosurveillance. Here, we report that the induction of retinoic acid early transcript 1 (RAE1) ligands for NKG2D by the DDR relies on a STING-dependent DNA sensor pathway involving the effector molecules TBK1 and IRF3. Cytosolic DNA was detected in lymphoma cell lines that express RAE1 and its occurrence required activation of the DDR. Transfection of DNA into ligand-negative cells was sufficient to induce RAE1 expression. Irf3(+/-);Eμ-Myc mice expressed lower levels of RAE1 on tumor cells and showed a reduced survival rate compared with Irf3(+/+);Eμ-Myc mice. Taken together, our results suggest that genomic damage in tumor cells leads to activation of STING-dependent DNA sensor pathways, thereby activating RAE1 and enabling tumor immunosurveillance.
The diversity of microbially mediated redox processes that occur in marine sediments is likely underestimated, especially with respect to the metabolisms that involve solid substrate electron donors ...or acceptors. Though electrochemical studies that utilize poised potential electrodes as a surrogate for solid substrate or mineral interactions have shed some much needed light on these areas, these studies have traditionally been limited to one redox potential or metabolic condition. This work seeks to uncover the diversity of microbes capable of accepting cathodic electrons from a marine sediment utilizing a range of redox potentials, by coupling electrochemical enrichment approaches to microbial cultivation and isolation techniques. Five lab-scale three-electrode electrochemical systems were constructed, using electrodes that were initially incubated in marine sediment at cathodic or electron-donating voltages (five redox potentials between −400 and −750 mV versus Ag/AgCl) as energy sources for enrichment. Electron uptake was monitored in the laboratory bioreactors and linked to the reduction of supplied terminal electron acceptors (nitrate or sulfate). Enriched communities exhibited differences in community structure dependent on poised redox potential and terminal electron acceptor used. Further cultivation of microbes was conducted using media with reduced iron (Fe
0
, FeCl
2
) and sulfur (S
0
) compounds as electron donors, resulting in the isolation of six electrochemically active strains. The isolates belong to the genera
Vallitalea
of the
Clostridia
,
Arcobacter
of the
Epsilonproteobacteria
,
Desulfovibrio
of the
Deltaproteobacteria
, and
Vibrio
and
Marinobacter
of the
Gammaproteobacteria
. Electrochemical characterization of the isolates with cyclic voltammetry yielded a wide range of midpoint potentials (99.20 to −389.1 mV versus Ag/AgCl), indicating diverse metabolic pathways likely support the observed electron uptake. Our work demonstrates culturing under various electrochemical and geochemical regimes allows for enhanced cultivation of diverse cathode-oxidizing microbes from one environmental system. Understanding the mechanisms of solid substrate oxidation from environmental microbes will further elucidation of the ecological relevance of these electron transfer interactions with implications for microbe-electrode technologies.
Introduction Adolescence is a key period of vulnerability for poor mental health as the brain is still developing and may be more sensitive to the negative impacts of stress and adversity. ...Unfortunately, few measures comprehensively assess wellbeing in adolescents. Methods The 26-item COMPAS-W Wellbeing Scale for adults was validated in a sample of 1,078 adolescents aged 13–17 years old (51.67% male, 79.13% non-clinical vs 20.87% psychiatric or developmental clinical cases). The six COMPAS-W sub-scales and total scale were examined in this sample using second-order confirmatory factor analysis, and psychometric testing. Results The 23-item COMPAS-W demonstrated the best fit for this sample according to goodness-of-fit indices (χ 2 (220, 1078) = 1439.395, p < 0.001, CFI = 0.893, TLI = 0.877, RMSEA = 0.070, SRMR = 0.095). Internal reliability for the confirmed 23-item COMPAS-W model was run for the total scale ( α = 0.912) and sub-scales (Composure, α = 0.735; Own-worth, α = 0.601; Mastery, α = 0.757; Positivity, α = 0.721; Achievement, α = 0.827; and Satisfaction, α = 0.867). Test-retest reliability over 6 weeks was also good for the total scale at r = 0.845 and the sub-scales: Composure ( r = 0.754), Own-worth ( r = 0.743), Mastery ( r = 0.715), Positivity ( r = 0.750), Achievement ( r = 0.750), and Satisfaction ( r = 0.812). Compared with non-clinical participants’ wellbeing ( M = 90.375, SE = 0.400), those with clinical diagnoses reported lower wellbeing, both for those with developmental diagnoses ( M = 85.088, SE = 1.188), or psychiatric diagnoses ( M = 78.189, SE = 1.758), or combined developmental and psychiatric diagnoses ( M = 77.079, SE = 2.116). Yet, when wellbeing category scores were considered by diagnosis group, both non-clinical and clinical groups demonstrated incidence across all three categories of languishing, moderate and flourishing wellbeing, in support of the dual-continua model of mental health. On average, younger adolescents’ (13–14 years) wellbeing did not differ from older adolescents’ (15–17 years) wellbeing; however, for sex, males scored 1.731 points significantly higher in wellbeing compared with females ( p = 0.028); and American participants scored 3.042 points significantly higher in wellbeing compared with Australian participants ( p < 0.001). Discussion In conclusion, the 23-item COMPAS-W is a reliable measure of wellbeing for adolescents, both for those with and without developmental and psychiatric diagnoses.
Chickens are the reservoir host of Salmonella Enteritidis. Salmonella Enteritidis colonizes the gastro-intestinal tract of chickens and replicates within macrophages without causing clinically ...discernable illness. Persistence of S. Enteritidis in the hostile environments of intestinal tract and macrophages allows it to disseminate extra-intestinally to liver, spleen, and reproductive tract. Extra-intestinal dissemination into reproductive tract leads to contamination of internal contents of eggs, which is a major risk factor for human infection. Understanding the genes that contribute to S. Enteritidis persistence in the chicken host is central to elucidate the genetic basis of the unique pathobiology of this public health pathogen. The aim of this study was to identify a succinct set of genes associated with infection-relevant in vitro environments to provide a rational foundation for subsequent biologically-relevant research. We used in silico prediction of gene expression and RNA-seq technology to identify a core set of 73 S. Enteritidis genes that are consistently highly expressed in multiple S. Enteritidis strains cultured at avian physiologic temperature under conditions that represent intestinal and intracellular environments. These common highly expressed (CHX) genes encode proteins involved in bacterial metabolism, protein synthesis, cell-envelope biogenesis, stress response, and a few proteins with uncharacterized functions. Further studies are needed to dissect the contribution of these CHX genes to the pathobiology of S. Enteritidis in the avian host. Several of the CHX genes could serve as promising targets for studies towards the development of immunoprophylactic and novel therapeutic strategies to prevent colonization of chickens and their environment with S. Enteritidis.
ABSTRACT
Acoustic neuroma, also known as vestibular schwannoma, is a rare benign brainstem tumour involving the abnormal growth and proliferation of Schwann cells surrounding the vestibular division ...of the eighth cranial nerve. Although the most common symptoms are non‐dentally related, there are instances where diagnosis of this potentially life‐threatening condition is triggered by an emergency presentation to the dentist for the most trivial of reasons. A 56‐year‐old male presented to a dental clinic complaining of a toothache. Following history taking, examination and radiographs a carious lower right molar was extracted. The patient reported relief but later described post‐extraction numbness on the opposite side (left) of his lower jaw that could not be explained by anatomical principles or previous dental history. Further investigations revealed an acoustic neuroma as the underlying cause. This case highlights that not all signs and symptoms that occur in the mouth are abnormalities within the mouth. In particular, this case underscores the importance of recognizing that the spontaneous onset of certain symptoms may be due to significant non‐dental pathology. Any numbness over the distribution of the trigeminal nerve must be investigated. The importance of the basic sciences and referring will also be emphasized.
Biofuels have been promoted as a renewable energy option in many countries, but have also faced extensive scrutiny over their sustainability. Food security is perhaps the most debated sustainability ...impact of biofuels, especially in regions such as Sub-Saharan Africa that experience high rates of malnutrition and have been a major destination for biofuel-related investments. This study assesses the local food security impacts of engagement in biofuel crop production using a consistent protocol between multiple crops and sites. We use standardized metrics of food security related to dietary diversity and perceptions of hunger, and focus on feedstock smallholders and plantation workers in four operational projects: a large-scale jatropha plantation (Mozambique), a smallholder-based jatropha project (Malawi) and two hybrid sugarcane projects (Malawi, Eswatini). Collectively these reflect the main feedstocks, modes of production and land use transitions related to biofuel projects in Sub-Sahara Africa. Inverse Probability Weighting analysis indicates that involvement in sugarcane production improved household food security for plantation workers and feedstock smallholders. Conversely, involvement in jatropha production does not have a statistically significant positive effect on household food security for both workers and smallholders. Regression models indicate that the factors driving food security indicator levels vary between study sites. Wealth indicators influence food security indicators in several sites, but the absolute level of income plays a smaller role, while income stability/regularity, access to credit and stable markets for selling sugarcane be important drivers as indicated by the strong effect of proxy variables on indicators.
•Assess local food security impacts of biofuel crop production in southern Africa.•The case studies reflect main crops, modes of production and types of engagement.•Engagement in sugarcane production has generally positive food security outcomes.•Engagement in jatropha production has no or slightly negative food security outcomes.
Objective
The longitudinal course of neuropsychological functioning after the first manic episode in bipolar disorder is unknown. The present study evaluated cognitive change in bipolar disorder in ...the first 3 years after the initial manic episode.
Methods
Ninety‐one newly diagnosed patients with bipolar disorder and 61 demographically similar healthy participants received a neuropsychological evaluation assessing multiple cognitive domains at baseline, 1‐year, and 3‐year time points. Patients also received clinical assessments including mood ratings at all time points.
Results
Patients showed deficits in all domains at baseline, but similar longitudinal trajectories across time relative to healthy participants in most cognitive domains. For processing speed, patients showed more gains than controls from baseline to 1 year, but these gains stabilized thereafter. Patients with alcohol/substance abuse showed an initial delay but subsequent recovery in executive functioning. Patients who discontinued antipsychotic treatment showed better cognitive outcomes in verbal memory.
Conclusion
Appropriately treated patients with bipolar disorder showed favorable cognitive outcome in the first 3 years after experiencing an initial manic episode, arguing against cognitive neuroprogression at this stage of the illness. Discontinuation of antipsychotic treatment may be associated with better cognitive outcomes, but clarification of the role of antipsychotics on cognitive functioning requires further investigation.
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