129 research outputs found
Generalised left ventricular dysfunction after traumatic right coronary artery - right atrial fistula
A patient with traumatic right coronary artery to right atrial fistula, which was repaired by direct closure and aortocoronary saphenous vein bypass grafting, is described. Cardiac catheterisation and selective cine angiocardiography were performed pre- and postoperatively, and left ventricular (LV) function was studied in detail by invasive and non-invasive techniques. There was regional (diaphragmatic) LV asynergy but also generalised impairment of myocardial function, and these abnormalities persisted after operation.S. Afr. Med. J., 48, 1829 (1974)
Lineage-specific RUNX3 hypomethylation marks the preneoplastic immune component of gastric cancer
Runt domain transcription factor 3 (RUNX3) is widely regarded as a tumour-suppressor gene inactivated by DNA hypermethylation of its canonical CpG (cytidine-phosphate-guanidine) island (CGI) promoter in gastric cancer (GC). Absence of RUNX3 expression from normal gastric epithelial cells (GECs), the progenitors to GC, coupled with frequent RUNX3 overexpression in GC progression, challenge this longstanding paradigm. However, epigenetic models to better describe RUNX3 deregulation in GC have not emerged. Here, we identify lineage-specific DNA methylation at an alternate, non-CGI promoter (P1) as a new mechanism of RUNX3 epigenetic control. In normal GECs, P1 was hypermethylated and repressed, whereas in immune lineages P1 was hypomethylated and widely expressed. In human GC development, we detected aberrant P1 hypomethylation signatures associated with the early inflammatory, preneoplastic and tumour stages. Aberrant P1 hypomethylation was fully recapitulated in mouse models of gastric inflammation and tumorigenesis. Cell sorting showed that P1 hypomethylation reflects altered cell-type composition of the gastric epithelium/tumour microenvironment caused by immune cell recruitment, not methylation loss. Finally, via long-term culture of gastric tumour epithelium, we revealed that de novo methylation of the RUNX3 canonical CGI promoter is a bystander effect of oncogenic immortalization and not likely causal in GC pathogenesis as previously argued. We propose a new model of RUNX3 epigenetic control in cancer, based on immune-specific, non-CGI promoter hypomethylation. This novel epigenetic signature may have utility in early detection of GC and possibly other epithelial cancers with premalignant immune involvement
Clinical features and molecular genetic analysis in a Turkish family with oral white sponge nevus
Oral white sponge nevus (WSN) is a rare autosomal dominant benign condition, characterized by asymptomatic spongy white plaques. Mutations in Keratin 4 (KRT4) and 13 (KRT13) have been shown to cause WSN. Familial cases are uncommon due to irregular penetrance. Thus, the aim of the study was: a) to demonstrate the clinical and histopathological features of a three-generation Turkish family with oral WSN b) to determine whether KRT4 or KRT13 gene mutation was the molecular basis of WSN. Out of twenty members of the family ten were available for assessment. Venous blood samples from six affected and five unaffected members and 48 healthy controls were obtained for genetic mutational analysis. Polymerase chain reaction was used to amplify all exons within KRT4 and KRT13 genes. These products were sequenced and the data was examined for mutations and polymorphisms. Varying presentation and severity of clinical features were observed. Analysis of the KRT13 gene revealed the sequence variant Y118D as the disease-causing mutation. One patient revealed several previously unreported polymorphisms including a novel mutation in exon 1 of the KRT13 gene and a heterozygous deletion in exon 1 of KRT4. This deletion in the KRT4 gene was found to be a common polymorphism reflecting a high allele frequency of 31.25% in the Turkish population. Oral WSN may manifest variable clinical features. The novel mutation found in the KRT13 gene is believed to add evidence for a mutational hotspot in the mucosal keratins. Molecular genetic analysis is required to establish correct diagnosis and appropriate genetic consultation
Loss of gastrokine-2 drives premalignant gastric inflammation and tumor progression
Chronic mucosal inflammation is associated with a greater risk of gastric cancer (GC) and, therefore, requires tight control by suppressive counter mechanisms. Gastrokine-2 (GKN2) belongs to a family of secreted proteins expressed within normal gastric mucosal cells. GKN2 expression is frequently lost during GC progression, suggesting an inhibitory role; however, a causal link remains unsubstantiated. Here, we developed Gkn2 knockout and transgenic overexpressing mice to investigate the functional impact of GKN2 loss in GC pathogenesis. In mouse models of GC, decreased GKN2 expression correlated with gastric pathology that paralleled human GC progression. At baseline, Gkn2 knockout mice exhibited defective gastric epithelial differentiation but not malignant progression. Conversely, Gkn2 knockout in the IL-11/STAT3-dependent gp130[superscript F/F] GC model caused tumorigenesis of the proximal stomach. Additionally, gastric immunopathology was accelerated in Helicobacter pyloriâinfected Gkn2 knockout mice and was associated with augmented T helper cell type 1 (Th1) but not Th17 immunity. Heightened Th1 responses in Gkn2 knockout mice were linked to deregulated mucosal innate immunity and impaired myeloid-derived suppressor cell activation. Finally, transgenic overexpression of human gastrokines (GKNs) attenuated gastric tumor growth in gp130[superscript F/F] mice. Together, these results reveal an antiinflammatory role for GKN2, provide in vivo evidence that links GKN2 loss to GC pathogenesis, and suggest GKN restoration as a strategy to restrain GC progression
Thermal and optical analysis of a passive heat recovery and storage system for greenhouse skin
The thermal performance of a greenhouse can be greatly affected by the thermal and optical properties of its envelope system. In this study, a novel skin for greenhouse consisting of ethene-co-tetrafluoroethene (ETFE) membrane and Phase Change Material (PCM) RT28 has been developed and has also been experimentally investigated. The optical behaviour of the developed ETFE-Phase Change Material module sample is measured using a spectrometer and a pyranometer, respectively. The results show that at liquid state, the module has higher transmittance than that of at solid state. In addition, the light transmittance is related to the PCM's temperature. In the thermal aspect, the ETFE-Phase Change Material module presents different characterisation under various irradiances. Comparative analysis is also conducted for the ETFE-Phase Change Material, ETFE-water and ETFE alone. The ETFE-Phase Change Material system shows a benefit of the thermal management than that of other systems
Surgical Management of Overfilling of a Root Canal Filling Material: a Case Report
U radu je predstavljeno kirurĆĄko lijeÄenje u sluÄaju kad su bol i oteklina bili uzrok izlaska materijala za punjenje korijenskog kanala u veliku periapikalnu leziju izmeÄu lateralnog sjekutiÄa i oÄnjaka lijeve maksile. Oteklina je bila bolna na dodir. Lezija i materijal kirurĆĄki su uklonjeni. Da je sve potpuno zacijelilo, zakljuÄeno je radioloĆĄki na postoperativnom pregledu godinu dana nakon zahvata. KirurĆĄka intervencija velikih periapikalnih lezija indicirana je ako se nehotice dogodi da izaÄu velike koliÄine materijala za punjenje korijenskih kanala, kako bi se omoguÄilo cijeljenje periradikularnog tkiva.The surgical treatment of a case presenting pain and swelling due to the extrusion of the root canal filling into a large periapical lesion between left maxillary lateral and canine teeth is presented in this report. The swelling was painful on palpation. Removal of the lesion and the material was made surgically. Complete healing was observed at the postoperative first year radiographically. Surgical intervention of large periapical lesions is indicated in cases in which the extrusion of large amount of root canal filling material occurred inadvertently to provide healing of the periradicular tissues
Stress fracture of bilateral tibial metaphysis due to ceremonial march training: a case report
Stress fractures are caused by repetitive microtraumas that occur during unusual or increased activities. Clinical suspicion is essential for the diagnosis. A twenty-years old soldier was presented with bilateral knee pain and restriction of knee movements after a period of training for ceremonial march. Although plain X-rays were normal, scintigraphy and MRI revealed stress fractures at metaphyseal region of both tibias. History of a patient presenting with persisting joint or bone pain after an unusual repetitive activity should be delicately inquired. Typical history, although pain might be localized to unusual sites, should raise the suspicion of a stress fracture
Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry
Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes
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