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Retrons are toxin-antitoxin systems protecting bacteria against bacteriophages via abortive infection. The Retron-Eco1 antitoxin is formed by a reverse transcriptase (RT) and a non-coding RNA (ncRNA)/multi-copy single-stranded DNA (msDNA) hybrid that neutralizes an uncharacterized toxic effector. Yet, the molecular mechanisms underlying phage defense remain unknown. Here, we show that the N-glycosidase effector, which belongs to the STIR superfamily, hydrolyzes NAD + during infection. Cryoelectron microscopy (cryo-EM) analysis shows that the msDNA stabilizes a filament that cages the effector in a low-activity state in which ADPr, a NAD + hydrolysis product, is covalently linked to the catalytic E106 residue. Mutations shortening the msDNA induce filament disassembly and the effector's toxicity, underscoring the msDNA role in immunity. Furthermore, we discovered a phage-encoded Retron-Eco1 inhibitor (U56) that binds ADPr, highlighting the intricate interplay between retron systems and phage evolution. Our work outlines the structural basis of Retron-Eco1 defense, uncovering ADPr's pivotal role in immunity., Competing Interests: Declaration of interests G.M. is a stockholder and member of the SAB of Ensoma, and M.R.M. is listed as co-inventor of patent application WO2023141602A2, related to the use of engineered retrons for genome editing., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) remains a major public health challenge that contributes greatly to mortality and morbidity worldwide. Although it has long been recognized that the epithelium is altered in COPD, there has been little focus on targeting it to modify the disease course. Therefore, mechanisms that disrupt epithelial cell function in patients with COPD are poorly understood. In this study, we sought to determine whether epigenetic reprogramming of the cell-cell adhesion molecule E-cadherin, encoded by the CDH1 gene, disrupts epithelial integrity. By reducing these epigenetic marks, we can restore epithelial integrity and rescue alveolar airspace destruction. We used differentiated normal and COPD-derived primary human airway epithelial cells, genetically manipulated mouse tracheal epithelial cells, and mouse and human precision-cut lung slices to assess the effects of epigenetic reprogramming. We show that the loss of CDH1 in COPD is due to increased DNA methylation site at the CDH1 enhancer D through the downregulation of the ten-eleven translocase methylcytosine dioxygenase (TET) enzyme TET1 . Increased DNA methylation at the enhancer D region decreases the enrichment of RNA polymerase II binding. Remarkably, treatment of human precision-cut slices derived from patients with COPD with the DNA demethylation agent 5-aza-2'-deoxycytidine decreased cell damage and reduced air space enlargement in the diseased tissue. Here, we present a novel mechanism that targets epigenetic modifications to reverse the tissue remodeling in human COPD lungs and serves as a proof of concept for developing a disease-modifying target.

Objectives: To determine the development rate of hepatocellular carcinoma and survival of patients diagnosed to have regenerative, and low-grade and high-grade dysplastic liver nodules., Design: Retrospective descriptive study., Setting: Acute public hospital, Hong Kong., Patients: Patients with non-malignant liver nodules confirmed by imaging-guided liver biopsy between January 1997 and December 2008., Main Outcome Measures: Rates of hepatocellular carcinoma development and survival., Results: A total of 147 patients with non-malignant liver nodules were followed up over a median duration of 29 months. The initial histological diagnosis included regenerative nodules (n=74), low-grade dysplastic nodules (n=34), and high-grade dysplastic nodules (n=39). The respective cumulative hepatocellular carcinoma development rate during the first, second, third, and fourth year were 3%, 5%, 9% and 12% for simple regenerative nodules, 29%, 35%, 38% and 44% for low-grade dysplastic nodules, and 38%, 41%, 51% and 51% for high-grade dysplastic nodules. The hepatocellular carcinoma development rate was highest in those with high-grade dysplastic nodules. Multivariate analysis showed that histological dysplastic changes were associated with increased alpha-fetoprotein levels and advanced age, which were both independent predictors of hepatocellular carcinoma development. Histological dysplastic changes, male sex, advanced age, prolonged prothrombin time, and ultrasound appearances were independent predictors of mortality., Conclusion: The presence of dysplastic change in liver nodules increased the risk of hepatocellular carcinoma development and death.

This paper assesses the feasibility of transcatheter embolisation of arteriovenous shunts in patients with hepatocellular carcinoma, and reviews available embolic agents, based on our experience and a literature review. From 2001 to 2007, 11 patients with unresectable hepatocellular carcinoma and significant arteriovenous shunts underwent transcatheter embolisation of liver arteriovenous shunts. The age range was 36 to 80 years. A total of 17 embolisations were performed using different embolic agents including absolute ethanol (n=11), histoacryl (n=1), coils (n=2), and polyvinyl alcohol particles (n=1). We reviewed the degree of shunt occlusion and the clinical outcomes. There were 15 arteriovenous shunts. Nine (60%) were arterioportal venous shunts and six were arteriohepatic venous shunts. Two were classified as 'simple' types, according to our protocol, and 13 were 'complex' types. More than 80% occlusion was achieved in 80% of the shunts. In the simple shunts, coil embolisation achieved complete occlusion. In complex shunts with multiple feeders and draining veins, liquid or particulate agents were required to achieve satisfactory occlusion. Managing arteriovenous shunts with embolisation was feasible. The choice of embolic agent should be based on good understanding of the underlying mechanism of the shunts and their angio-architecture.

Inflammatory myofibroblastic tumor (IMT) is a rare tumor with a variable natural history and biologic behavior, ranging from completely benign to malignant with fatal outcome. We report a case of benign IMT in the left nasal cavity with radiologic features mimicking angiofibroma. We also demonstrate the hypervascular nature of this disease on angiography and the contribution of preoperative embolization in assisting surgical excision and minimizing the potential uncontrolled intraoperative bleeding.

Severe acute respiratory syndrome (SARS) is an emerging infectious disease with both pulmonary and extra-pulmonary manifestations. Although coagulation abnormalities are common in these patients, clinically overt thromboembolic events are rarely reported. This report describes the first case of pulmonary artery thrombosis in a patient with laboratory confirmed SARS.

Aim: To assess the efficacy of using ultrasonography (USG) in monitoring the progress of exit site infection (ESI) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD)., Methods: Twenty-two cases of newly diagnosed ESI and 20 cases with normal exit sites as controls were assessed by using USG. The exit sites were reassessed by using USG after finishing a course of antibiotic therapy, and the sonographic findings were correlated with the clinical outcome., Results: Out of the 22 cases of ESI, 21 cases had definite sonolucent zones around the external cuffs, while one case had normal sonographic findings. Of the 20 control cases of normal exit sites, 16 had normal sonographic findings, and four had sonolucent zones around the external cuffs. Exit site infections correlated with positive sonographic findings as compared to normal exits (P <0.0001). The 21 cases of ultrasonic-positive ESI were re-examined after antibiotic therapy, and 10 of these had a post-treatment sonolucent rim around the distal cuff < or =1 mm thick, while 11 cases were persistently > mm thick. The former group was shown to have a more favourable outcome (P=0.013). And despite variable USG findings, all eight patients with Pseudomonas aeruginosa-related ESI had an unfavourable clinical outcome., Conclusion: Ultrasonography of the exit sites in CAPD patients is a useful adjunctive tool in the management of ESI. A sonolucent zone around the external cuff >1 mm thick following a course of antibiotic treatment and the involvement of the proximal cuff are associated with poor clinical outcome. In ESI caused by Pseudomonas aeruginosa, the clinical outcome was uniformly poor irrespective of the sonographic findings.

Inferior vena caval (IVC) filter thrombosis in patients with contraindications to anticoagulant therapy is a difficult and challenging clinical problem. We report our experience in treating three such patients using a mechanical thrombectomy device, which resulted in rapid symptomatic relief until anticoagulant therapy could be safely introduced.

Unlabelled: To determine the optimal method of suprapubic aspiration (SPA), the success rates of real-time ultrasound-guided SPA were compared with those of conventional SPA, and factors associated with success were studied. Thirty infants were randomly allocated to group A (for real-time ultrasound-guided SPA) and 30 infants to group B (for blind SPA with a prehydration protocol). The results showed that the overall success rates for all attempts were similar (26/30 or 87% in group A vs 24/30 or 80% in group B, p > 0.05). The first attempts in both groups were equally successful (both 18/30 or 60%). In comparison with failed attempts, successful ultrasound SPA attempts were associated with a greater bladder depth (mean +/- SD: 28 +/- 11 vs 21 +/- 5 mm, p < 0.01), length (32 +/- 12 vs 23 +/- 9 mm, p < 0.05) and volume (17 +/- 13 vs 8 +/- 6 ml, p < 0.01), but similar width (33 +/- 9 vs 29 +/- 5 mm, p > 0.05). In blind SPA, successful attempts were associated with the presence of bladder dullness on percussion (odds ratio 29)., Conclusion: This study confirms that ultrasound-guided SPA has a high success rate. Blind SPA could also be equally successful with appropriate preparation. Ultrasound-guided SPA is recommended when the bladder depth exceeds 3 cm, or the bladder length exceeds 3.7 cm. If an ultrasound machine is not available, blind SPA may be an alternative, with attention being paid to prehydration and the demonstration of bladder dullness by percussion.

Late temporal lobe necrosis is a well-known and serious complication in patients with nasopharyngeal carcinoma (NPC) following radiotherapy. Owing to the close proximity to the skull base, the medial temporal lobes are inevitably included in the target volume of irradiation. Patients with NPC provide a unique opportunity in study of delay radiation effect in normal human brain. The objective of this study was to evaluate late temporal lobe radiation injury by combined multi-section diffusion weighted and perfusion weighted MR imaging. We prospectively studied 16 patients with typical clinical symptoms of late temporal lobe necrosis or other abnormalities in the temporal lobes incidentally detected by conventional MR imaging. All patients had a previous history of radiotherapy for histologically proven NPC. Conventional T1- and T2-weighted images, fast gradient echo with echo-planar diffusion-weighted and perfusion-weighted MR imaging were performed. Apparent diffusion coefficient (ADC) map and relative cerebral blood volume (rCBV) map were computed via commercially available software. MR diffusion and perfusion images were then analyzed and graded by two independent observers with focusing on the diffusion and perfusion mismatch. The temporal lobe lesions displayed marked high diffusion on the ADC map. The rCBV map also revealed marked hypoperfusion in these temporal lobe lesions in all patients. The areas of abnormality on the rCBV map were significantly larger than the lesions on the ADC map in 14 patients (observer 1) and 13 patients (observer 2). Since late temporal lobe necrosis is probably caused by damage of the endothelium of vessels and ischemia, perfusion and diffusion mismatch might imply injured tissue but potentially salvageable brain tissue. A mismatch may be potentially used to predict the response to treatment in-patients with late temporal lobe necrosis.

Background: We evaluated the ability of diffusion-weighted (DW) magnetic resonance (MR) imaging to differentiate between hepatic abscess and cystic or necrotic liver tumor., Methods: DW MR imaging was performed in 18 patients who had liver masses with large cystic or necrotic cavities detected by computed tomography or ultrasonography. The final diagnoses were pyogenic abscess (five cases), fungal abscess (one), hepatocellular carcinoma (five), cystic metastasis (four), and hepatic cyst (three). Signal intensities on the DW images and apparent diffusion coefficient (ADC) maps were noted. ADCs in all lesions were calculated and compared with Student's t test., Results: All lesions, except hepatic cysts, showed either heterogeneous or homogeneous rim enhancement on postgadolinium images. All abscess cavities showed hyperintensity on DW images and hypointensity on ADC maps. Conversely, the cystic or necrotic portions of all tumors showed hypointensity on DW images and hyperintensity on ADC maps. The mean ADCs (mm(2)/s) were 0.67 +/- 0.35 x 10(-3) in hepatic abscess, 2.65 +/- 0.49 x 10(-3) in cystic or necrotic tumor, 2.93 +/- 0.52 x 10(-3) in hepatic cyst, and 1.98 +/- 0.37 x 10(-3) in normal liver parenchyma., Conclusion: DW MR imaging, with the help of ADCs, may be a useful noninvasive imaging technique in differentiating hepatic abscess from cystic or necrotic tumor.

The objective of the study was to evaluate the capability and reliability of the magnetic resonance (MR) diffusion-weighted imaging (DWI) in differentiation between hydronephrosis and pyonephrosis. Single-shot echoplanar MR diffusion-weighted imaging was performed in 12 patients who had dilatation of the renal pelvis and calyces detected by ultrasonography (US). Microbiological tests confirmed that there were four cases of pyonephrosis and eight cases of hydronephrosis. Signal intensities of the collecting (pelvicalyceal) systems on the diffusion-weighted images and apparent diffusion coefficient (ADC) maps were noted. ADC values of the pelvicalyceal system in all patients were computed and compared using Student's t test. On diffusion-weighted images, the pelvicalyceal system of the hydronephrotic kidney was hypointense while the pelvicalyceal system of the pyonephrotic kidney was markedly hyperintense. The mean ADCs of the hydronephrotic and pyonephrotic renal pelvis were 2.98 +/- 0.65 x 10(-3) and 0.64 +/- 0.35 x 10(-3) mm(2)/s, respectively. The extremely low ADC of the renal pelvis of the pyonephrotic kidney accounted for its signal hyperintensity on diffusion-weighted images as well as signal hypointensity on ADC maps. In conclusion, the MR diffusion-weighted imaging may be a reliable tool to differentiate pyonephrosis from hydronephrosis.

We report the case history of a patient with a sphenoid sinus mucocoele detected by computed tomography and medical resonance imaging. The patient had a history of nasopharyngeal carcinoma, which was treated by radiotherapy more than 10 years previously. He presented with bilateral twelfth and sixth cranial nerve palsies. Local tumour recurrence was suspected. Further investigations showed that the cranial nerve palsies were caused by radiation damage and the sphenoid sinus mucocoele was an incidental finding. Sphenoid sinus mucocoele is a possible rare late complication of radiotherapy in patients with nasopharyngeal carcinoma.

The objective of this study was to evaluate the therapeutic effectiveness of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI). Seventeen patients with histopathologically proven HCC were included in this study. All patients underwent MR examinations with conventional T1- and T2-weighted images, gadolinium-enhanced images, and DSC-MRI before TACE treatment. Hepatic blood volume (HBV) maps were reconstructed from the time-intensity curves. The same MRI sequences and techniques were repeated 24 h and 6 weeks after TACE. Serial changes in tumor perfusion on HBV maps were correlated with vascularity in hepatic angiography. All tumors were hypointense on T1-weighted images and hyperintense on T2-weighted images. Heterogeneous enhancement was observed in all tumors before and immediately after TACE. Hyperperfusion was noted in most of the tumors on HBV map before TACE and moderate to marked hypoperfusion following TACE. The degree of tumor perfusion on HBV map correlated well with the vascularity in angiography. In conclusion, the noninvasive nature of DSC-MRI is useful to evaluate the effectiveness of TACE. Invasive procedures, such as angiography, are seldom necessary.

Background: We investigated the feasibility of using intravenous magnetic resonance (MR) contrast agent as a gastrointestinal oral negative contrast agent to null the bowel signal during MR cholangiopancreatography (MRCP)., Methods: In the first part of the study, a phantom study was performed to select the optimal concentration of MR contrast agent to be used as an oral negative contrast agent in MRCP. In the second part of the study, 23 consecutive patients suffering from different pancreaticobiliary diseases were imaged with a single-shot fast spin-echo pulse sequence. The data acquisition was started without oral contrast agent and then repeated with oral contrast agent. From the MR images taken with and without oral contrast agent, the gallbladder, cystic duct, common bile duct, and pancreatic duct were assessed and graded by two radiologists., Results: The oral contrast agent was tolerated well by all patients. In all patients the high signal intensity from the intestinal fluid was completely suppressed. The depictions of the gallbladder and cystic duct were slightly and moderately improved, respectively, whereas the depictions of the common bile duct and pancreatic duct were markedly improved by the oral contrast agent administration., Conclusion: Diluted intravenous MR contrast agent can be an effective and safe oral negative contrast agent in eliminating signal intensity of the gastrointestinal tract, thus improving the depiction of the biliary system in MRCP.

We examined nine patients with histologically proven nasopharyngeal carcinoma (NPC), treated with radiotherapy, using dynamic susceptibility contrast MRI (DSC-MRI). In eight there was clinical evidence of radionecrosis of the temporal lobe, and one was examined for local recurrence in the nasopharynx. All patients had either high-signal finger-like or cystic lesions in the temporal lobes on T2-weighted images. Heterogeneous contrast enhancement occurred in all patients. Relative regional cerebral blood volume (rrCBV) mapping revealed marked hypoperfusion in all patients. One underwent bilateral temporal lobectomy and radionecrosis was confirmed histologically.

OBJECTIVE: To study the characteristics of the shaken baby syndrome from 10 cases in Hong Kong. DESIGN: Retrospective study. SETTING: Regional public hospital, Hong Kong. PATIENTS: Six boys and four girls (mean age, 0.54 years; range, 0.18-1.42 years) in whom the shaken baby syndrome was diagnosed between January 1994 and June 1998. MAIN OUTCOME MEASURES: Clinical features at presentation, radiological findings, management, and outcome. RESULTS: All 10 patients presented with coma: the mean score on the Glasgow coma scale was 4.8 (range, 3-10). In all 10 cases, the history provided by the carers were incompatible with the patient's presentation. Nine patients presented with seizures. Retinal haemorrhages were detected in all patients, but peripheral signs of bruising were observed in only three. Acute subdural haematoma was found in eight patients; one of the remaining two children had subarachnoid and subdural haemorrhages, whereas the other had subarachnoid and intracerebral haemorrhages. Skeletal fractures were detected in two patients. The suspected abusers included either or both parents (n=3), childminders (n=3), and maids (n=2); the identity of the abusers were unknown in two cases. Prosecution by the police was initiated in three cases and two abusers were found to be guilty. Three children died of the abuse; the seven survivors had significant neurological handicaps. CONCLUSION: Medical practitioners should be alert to the occurrence of abusive head injury in children. Peripheral signs are uncommon and a high degree of suspicion is needed for the management to be successful.

Aims: The purpose of this study was to assess the value of breath-hold 3D gadolinium-enhanced subtraction magnetic resonance angiography (GD-MRA) in the detection of transplant renal artery stenosis (TRAS)., Patients and Methods: Seven patients with suspected post-transplant renal artery stenosis were studied. GD-MRA was performed at 1.5T with a 3D fast spoiled gradient recalled echo (FSPGR) pulse sequence. Before injection of contrast medium, the 3D pulse sequence was performed to obtain a set of non-contrast images for subtraction purposes. Dynamic 3D imaging was performed simultaneously with the bolus injection of 40 ml of gadopentetate dimeglumine. Angiographic images were reconstructed using the Advantage Window workstation (version 2.0 GE Medical Systems) and subtraction was made with the pre-contrast image data. Any signal intensity cut-off or narrowing of more than 50% was regarded as significant stenosis. Ultrasound Doppler (USD) study was performed with both colour and spectral studies. Peak systolic velocity (PSV) of greater than 2.0 m/s and acceleration time (AT) greater than 120ms was regarded as positive for TRAS. These were then compared with the digital subtraction angiography (DSA) as the gold standard., Results: A total of nine examinations performed in seven patients were included in the analysis. MRA correlated with the DSA findings in eight examinations, with one false negative. USG correlated with DSA in six examinations, with two false negative and one false positive case., Conclusion: In our opinion, GD-MRA is a promising and non-invasive technique in the detection of TRAS.

The aim of the study was to evaluate the usefulness of the magnetic resonance (MR) perfusion maps in the detection of liver tumor perfusion following transcatheter arterial chemoembolization (TACE). MR dynamic susceptibility contrast-enhanced imaging was performed in 12 patients with 10 confirmed hepatocellular carcinoma and 2 confirmed hepatic metastasis using single-shot echoplanar pulse sequence. Time-intensity curves for all hepatic tumors showed a transient signal drop and the hepatic blood volume (HBV) maps were reconstructed. On the HBV maps, most tumors (80%) demonstrated hyperperfusion before TACE and hypoperfusion following TACE. The site and the degree of residual hyperperfusion within the tumor on the HBV maps correlated well with the areas of hypervascularity on the angiograms. In conclusion, the MR perfusion maps can be a promising technique for detecting the perfusion of the residual tumor tissue following TACE.