Investigating postharvest chilling injury in tomato (Solanum lycopersicum L.) fruit using magnetic resonance imaging and 5-azacytidine, a hypomethylation agent

Tomato, like most species from tropical and subtropical regions, exhibits postharvest chilling injury (PCI) when stored at low temperatures. Because of its economic importance and the functional genomics tools available, we used tomato to investigate aspects of fruit PCI development. We asked two questions: First, are there spatial-temporal differences in the development of PCI that can be detected by magnetic resonance imaging (MRI)? Here, the aim was to use a non-invasive method to study PCI progression in vivo. At mature green and breaker, the pericarp, locular tissue and columella produced distinct D-values while in contrast, there was no such differentiation in riper fruit. Although the pericarp is where most PCI symptoms are visible, this tissue showed less dynamism upon cold exposure, compared to the inner tissues as detected by MRI. This suggests the occurrence of distinct, independently modulated mechanisms contributing to the development of PCI-symptomatology. Collectively our data showed that the MRI could detect fruit ripening, its attenuation by cold, and fruit tissue-specific responses to chilling stress. The second question we asked was if epigenetic modification of the tomato genome or transcriptome influences PCI response. We examined PCI severity in fruit injected with a demethylating agent, 5- azacytidine (AZA). Two tomato genotypes exposed to varying severities of cold-stress were studied. Results suggested that AZA was able to moderate PCI in 'Micro-Tom' after 3 weeks at 2.5°C, while different patterns were observed in 'Sun Cherry' across various cold treatments. The effects of AZA on PCI were complex, multilayered and highly context-dependent

Infarct size and left ventricular remodelling after preventive percutaneous coronary intervention

Objective: We hypothesised that, compared with culprit-only primary percutaneous coronary intervention (PCI), additional preventive PCI in selected patients with ST-elevation myocardial infarction with multivessel disease would not be associated with iatrogenic myocardial infarction, and would be associated with reductions in left ventricular (LV) volumes in the longer term. Methods: In the preventive angioplasty in myocardial infarction trial (PRAMI; ISRCTN73028481), cardiac magnetic resonance (CMR) was prespecified in two centres and performed (median, IQR) 3 (1, 5) and 209 (189, 957) days after primary PCI. Results: From 219 enrolled patients in two sites, 84% underwent CMR. 42 (50%) were randomised to culprit-artery-only PCI and 42 (50%) were randomised to preventive PCI. Follow-up CMR scans were available in 72 (86%) patients. There were two (4.8%) cases of procedure-related myocardial infarction in the preventive PCI group. The culprit-artery-only group had a higher proportion of anterior myocardial infarctions (MIs) (55% vs 24%). Infarct sizes (% LV mass) at baseline and follow-up were similar. At follow-up, there was no difference in LV ejection fraction (%, median (IQR), (culprit-artery-only PCI vs preventive PCI) 51.7 (42.9, 60.2) vs 54.4 (49.3, 62.8), p=0.23), LV end-diastolic volume (mL/m2, 69.3 (59.4, 79.9) vs 66.1 (54.7, 73.7), p=0.48) and LV end-systolic volume (mL/m2, 31.8 (24.4, 43.0) vs 30.7 (23.0, 36.3), p=0.20). Non-culprit angiographic lesions had low-risk Syntax scores and 47% had non-complex characteristics. Conclusions: Compared with culprit-only PCI, non-infarct-artery MI in the preventive PCI strategy was uncommon and LV volumes and ejection fraction were similar

The Broad Spectrum HDAC Inhibitor PCI-24781 Induces Caspase- and ROS-Dependent Apoptosis and is Synergistic with Bortezomib in Lymphoma

We investigated the cytotoxicity and biology of the novel broad-spectrum hydroxamic acid-based histone deacetylase inhibitor (HDACi), PCI-24781. PCI-24781 was studied alone and combined with bortezomib in Hodgkin lymphoma (L428) and non-Hodgkin's lymphoma cell lines (Ramos, HF1, SUDHL4). PCI-24781 induced dose-dependent apoptosis that was associated with prominent G0/G1 arrest, decreased S-phase, increased p21 protein expression, and production of reactive oxygen species (ROS). Furthermore, PCI-24781-induced apoptosis was shown to be ROS- and caspase-dependent. Combined PCI-24781 and bortezomib exposure resulted in strong synergistic apoptosis in all cell lines (combination indices 0.19-0.6). Furthermore, compared to either agent alone, PCI-24781/bortezomib resulted in increased caspase cleavage, mitochondrial depolarization, and histone hyperacetylation. Microarray analyses showed that PCI-24781 alone significantly downregulated several antioxidant genes, proteasome components, and NF-kappaB pathway genes, effects which were enhanced further with bortezomib. RT-PCR confirmed downregulation of NF-kappaB targets NF-kappaB1 (p105), c-Myc, and IkappaB-kinase subunits, while gel-shift showed decreased NF-kappaB DNA-binding activity. Taken together, these results suggest that increased oxidative stress and NF-kappaB inhibition, leading to caspase activation and apoptosis, are likely responsible for the activity of PCI-24781 as well as the observed synergy with bortezomib. These data indicate that PCI-24781 has potential therapeutic value in lymphoma as a single-agent and combined with bortezomib

Medical therapy, percutaneous coronary intervention and prognosis in patients with chronic total occlusions

Objective There is little published data reporting outcomes for those found to have a chronic total coronary occlusion (CTO) that is electively treated medically versus those treated by percutaneous coronary intervention (PCI). We sought to compare long-term clinical outcomes between patients treated by PCI and elective medical therapy in a consecutive cohort of patients with an identified CTO. Methods Patients found to have a CTO on angiography between January 2002 and December 2007 in a single tertiary centre were identified using a dedicated database. Those undergoing CTO PCI and elective medical therapy to the CTO were propensity matched to adjust for baseline clinical and angiographic differences. Results In total, 1957 patients were identified, a CTO was treated by PCI in 405 (20.7%) and medical therapy in 667 (34.1%), 885 (45.2%) patients underwent coronary artery bypass graft surgery. Of those treated by PCI or medical therapy, propensity score matching identified 294 pairs of patients, PCI was successful in 177 patients (60.2%). All-cause mortality at 5 years was 11.6% for CTO PCI and 16.7% for medical therapy HR 0.63 (0.40 to 1.00, p=0.052). The composite of 5-year death or myocardial infarction occurred in 13.9% of the CTO PCI group and 19.6% in the medical therapy group, HR 0.64 (0.42 to 0.99, p=0.043). Among the CTO PCI group, if the CTO was revascularised by any means during the study period, 5-year mortality was 10.6% compared with 18.3% in those not revascularised in the medical therapy group, HR 0.50 (0.28–0.88, p=0.016). Conclusions Revascularisation, but not necessarily PCI of a CTO, is associated with improved long-term survival relative to medical therapy alone

Elective percutaneous coronary intervention in the elderly patient

Elderly patients account for an increasing number and proportion of patients requiring management of coronary artery disease. Whilst medical therapy remains the cornerstone of management, percutaneous coronary intervention (PCI) has been shown to improve symptoms of angina and quality of life in elderly patients. PCI is now a routine treatment for both acute and chronic coronary artery disease. In the last decade, a series of technological and therapeutic developments have reduced in-hospital complications following PCI. The transradial approach is associated with fewer vascular complications, reduced bed utilization and reduced time to ambulation. This has facilitated the introduction and expansion of outpatient PCI, which has been shown to be safe and effective in elderly patients. This article reviews the rationale for outpatient PCI in the elderly and the evidence for its effectiveness and safety

Impact of proctoring on success rates for percutaneous revascularisation of coronary chronic total occlusions.

OBJECTIVE: To assess the impact of proctoring for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in six UK centres. METHODS: We retrospectively analysed 587 CTO procedures from six UK centres and compared success rates of operators who had received proctorship with success rates of the same operators before proctorship (pre-proctored) and operators in the same institutions who had not been proctored (non-proctored). There were 232 patients in the pre-proctored/non-proctored group and 355 patients in the post-proctored group. Complexity was assessed by calculating the Japanese CTO (JCTO) score for each case. RESULTS: CTO PCI success was greater in the post-proctored compared with the pre-proctored/non-proctored group (77.5% vs 62.1%, p<0.0001). In more complex cases where JCTO≥2, the difference in success was greater (70.7% vs 49.5%, p=0.0003). After proctoring, there was an increase in CTO PCI activity in centres from 2.5% to 3.5%, p<0.0001 (as a proportion of total PCI), and the proportion of very difficult cases with JCTO score ≥3 increased from 15.3% (35/229) to 29.7% (105/354), p<0.0001. CONCLUSIONS: Proctoring resulted in an increase in procedural success for CTO PCI, an increase in complex CTO PCI and an increase in total CTO PCI activity. Proctoring may be a valuable way to improve access to CTO PCI and the likelihood of procedural success

A coded-aperture technique allowing x-ray phase contrast imaging with conventional sources

Phase contrast imaging (PCI) solves the basic limitation of x-ray imaging, i.e., poor image contrast resulting from small absorption differences. Up to now, it has been mostly limited to synchrotron radiation facilities, due to the stringent requirements on the x-ray source and detectors, and only one technique was shown to provide PCI images with conventional sources but with limits in practical implementation. The authors propose a different approach, based on coded apertures, which provides high PCI signals with conventional sources and detectors and imposes practically no applicability limits. They expect this method to cast the basis of a widespread diffusion of PCI. (C) 2007 American Institute of Physics

The effect of age on outcomes of coronary artery bypass surgery compared with balloon angioplasty or bare-metal stent implantation among patients with multivessel coronary disease. A collaborative analysis of individual patient data from 10 randomized trials.

OBJECTIVES: This study sought to assess whether patient age modifies the comparative effectiveness of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI). BACKGROUND: Increasingly, CABG and PCI are performed in older patients to treat multivessel disease, but their comparative effectiveness is uncertain. METHODS: Individual data from 7,812 patients randomized in 1 of 10 clinical trials of CABG or PCI were pooled. Age was analyzed as a continuous variable in the primary analysis and was divided into tertiles for descriptive purposes (≤56.2 years, 56.3 to 65.1 years, ≥65.2 years). The outcomes assessed were death, myocardial infarction and repeat revascularization over complete follow-up, and angina at 1 year. RESULTS: Older patients were more likely to have hypertension, diabetes, and 3-vessel disease compared with younger patients (p < 0.001 for trend). Over a median follow-up of 5.9 years, the effect of CABG versus PCI on mortality varied according to age (interaction p < 0.01), with adjusted CABG-to-PCI hazard ratios and 95% confidence intervals (CI) of 1.23 (95% CI: 0.95 to 1.59) in the youngest tertile; 0.89 (95% CI: 0.73 to 1.10) in the middle tertile; and 0.79 (95% CI: 0.67 to 0.94) in the oldest tertile. The CABG-to-PCI hazard ratio of less than 1 for patients 59 years of age and older. A similar interaction of age with treatment was present for the composite outcome of death or myocardial infarction. In contrast, patient age did not alter the comparative effectiveness of CABG and PCI on the outcomes of repeat revascularization or angina. CONCLUSIONS: Patient age modifies the comparative effectiveness of CABG and PCI on hard cardiac events, with CABG favored at older ages and PCI favored at younger ages

Door-to-balloon time in primary percutaneous coronary intervention for patients with ST-Segment Elevation Myocardial Infarction

Introduction: Over the past years Primary Percutaneous Coronary Intervention (PCI) has emerged as an effective treatment strategy for acute ST-Elevation Myocardial Infarction (STEMI).1 The survival rate with Primary PCI however is dependent on the time to treatment,2 thus, given the time dependency of survival in patient with STEMI undergoing Primary PCI, the American College of Cardiology and American Heart Association (ACC/AHA) in their management guidelines of acute myocardial infarction also endorsed by European Society of Cardiology (ESC) have established a door- to-balloon time of 90 minutes as a gold standard for Primary PCI.4 The aim of this audit is to measure and compare this key performance measurement for quality of care of patients with STEMI in the Maltese Islands. Methods: This audit was conducted at the only PCI-capable hospital in Malta – Mater Dei Hospital. All the patients coming in through the Accident and Emergency Department with an ST-elevation Myocardial Infarction or a new onset Left Bundle Branch Block (LBBB), thus eligible for a Primary PCI, were included in this audit. This was a prospective audit between January 2012 and December 2012 and using a proforma, data was collected primarily to map out the Door-to-Ballon times for Primary PCI during that period. This data was also used to pinpoint areas were time delays occur when dealing with STEMI cases. Door-to-Balloon times from pre-hospital diagnosis of STEMI using the MRX was also audited and compared to times of in-hospital STEMI diagnosis. Results: During the 12 months duration of the audit, 157 patients were recorded in the CathLab Database as having had an Emergency Primary PCI. Recorded in the audit were 135 patients of which 123 were STEMI patients eligible for a Primary PCI and 12 STEMI patients not eligible for Primary PCI and thus not included in the audit. The Mean Door-to- Balloon times of all 123 patients was found to be 101.45 minutes. Data analysis showed that the times during 'Office Hours' (8am to 5pm) were statistically significantly less than those of 'After hours' (5pm to 8am) (N=123, p<0.001) and those with a Door-to- Balloon time of more than 90 minutes, data analysis showed the number of such cases were statistically significantly less during 'Office Hours' (N=36, p=0.02). With pre-hospital ECG diagnosis of STEMI, data analysis showed that with MRX, Door-to-Ballon times are significantly less when compared to those during 'Office Hours' and 'After Hours' (N=57, p=0.003 and N=66, p<0.001 respectively). Conclusion: From the results obtained, local achievement to remain well within the standards suggested by the ACC/AHA and ESC of Primary PCI ? 90 minutes for STEMI was not reached, however several factors contributing to delays and strategies to minimize delay were pointed out in order to further improve the local practice and thus lowering mortality rates associated with STEMI.peer-reviewe