Challenges and opportunities for cardiovascular disease prevention

Cardiovascular diseases are highly preventable, yet they remain the most common cause of death in the world. The epidemic is receding in industrialized countries; however, many low-income and middle-income countries have experienced an increase in cardiovascular diseases and 80% of all cardiovascular diseases deaths occur there. In the last 20 years, the epidemiology and surveillance of cardiovascular diseases have laid the foundations for public health interventions that may reduce the burden of disease. Relevant population-specific local data are therefore needed to describe the trends and pattern of risk for atherosclerotic diseases. Once the basis for surveillance and epidemiological research has been laid, cardiovascular disease prevention will require approaches adapted for each individual and population. The existence of effective preventive interventions justifies the assertion that coronary heart disease and stroke could be virtually prevented and controlled. Our goal in this review is to summarize the current challenges and opportunities for cardiovascular medicine, focusing on the need for high-quality local surveillance systems that provide the appropriate data needed to develop sound national cardiovascular disease preventive policies.     

Phase 1 study of epigenetic priming with decitabine prior to standard induction chemotherapy for patients with AML

We conducted an open-label phase 1 study exploring the feasibility, safety, and biologic activity of epigenetic priming with decitabine before standard induction chemotherapy in patients with less-than-favorable risk of acute myelogenous leukemia (AML). We directly compared the clinical and DNA-hypomethylating activity of decitabine delivered at 20 mg/m2 by either a 1-hour infusion (Arm A) or a continuous infusion (Arm B) for 3, 5, or 7 days before a single, standard induction with infusional cytarabine (100 mg/m2 for 7 days) and daunorubicin (60 mg/m2 × 3 doses). Toxicity was similar to that of standard induction chemotherapy alone. Although we did not identify a maximum tolerated dose, there was more gastro-intestinal toxicity with 7 days of decitabine priming. Decitabine induced DNA hypomethylation at all dose levels and there was a trend toward greater hypomethylation in CD34(+) bone marrow cells when decitabine was delivered by a short pulse (Arm A). Twenty-seven subjects (90%) responded to therapy: 17 with complete remission (57%) and 10 with partial remission (33%). Of the patients with partial remission to protocol treatment, 8 achieved remission to their next therapy, bringing the overall complete remission rate to 83%. We conclude that epigenetic priming of intensive chemotherapy can be safely delivered in an attempt to improve response rates. This trial was registered at www.clinicaltrials.gov as NCT00538876.     

Profile of sight‐threatening infectious keratitis: a prospective study

Purpose: To prospectively study patients presenting with sight‐threatening corneal ulcers with a view to identify the predisposing factors, causative organisms, clinical signs and treatment outcomes. Methods: Prospectively, over 3‐year period, all cases with serious infective keratitis presenting to Queens Medical Hospital in Nottingham, UK, were recruited. Detailed information on the aetiology, culture results, signs & symptoms, the treatment given and the patient’s response was collected and statistically analysed. Results: One hundred and forty‐three eyes of 129 patients were enrolled. Thirty‐one patients were managed as out‐patients, and 98 were treated as in‐patients. The mean duration of admission was 9 ± 13 days but was significantly higher in older patients and in Acanthamoeba keratitis cases. The important risk factors were ocular surface disease (32%), contact lens wear (26%) and previous ocular surgery (20%). Old age, deep infiltration, steroid use and poor initial vision were risk factors for prolonged course of treatment in bacterial keratitis. Corneal scrapings were done in 89% of the cases, but positive results were obtained only in 41.7%. Staphylococcus aureus was the most common isolated bacteria (18.8%). Acanthamoeba and Pseudomonas aeruginosa were the second and third common causative organisms (16.6% and 15%, respectively). Overall, 8.3% needed corneal grafting, which survived in 83.3% and eradicated infection in 100%. Conclusion: Microbial keratitis is an important cause of ocular morbidity. Previous ocular disease is an important predisposing factor. Old age, steroid use and poor presenting visual acuity are important prognostic indicators. Corneal grafting is an effective option for managing recalcitrant corneal infections.     

Predictive Value of sGaw,FEF25 − 75, and FEV1 for Development of Asthma after a Negative Methacholine Challenge Test

Background. A 20% change in forced expiratory volume in 1 second (FEV₁) during methacholine challenge testing (MCT) is a reliable marker of asthma. When the FEV₁ decrease is < 20%, there is controversy whether other changes in flows and conductance may be useful. We conducted this study to determine whether changes in sGaw, FEF_{25 ? 75}, and FEV₁ in a negative MCT could predict future occurrence of asthma over a 3-year period. Methods. A total of 100 consecutive patients with clinical suspicion of asthma but who had a negative MCT per ATS FEV₁ criteria (< 20% FEV₁ decline at 16 mg/mL of methacholine) performed by the 5-breath dosimeter method were analyzed. Two pulmonary fellows, blinded to MCT results, reviewed the patients' medical records. Patients were classified into one of three categories: asthmatic, unclear, and not asthmatic. Decreases in sGaw, FEF_{25 ? 75}, and FEV₁ in the five groups were then retrieved. Analysis of variance (ANOVA) was used for data analysis. Results. Of 100 patients, 23 were excluded owing to lack of a 3-year follow-up. After complete data review, the number of patients (n) in each group was as follows: asthmatic (n = 15), unclear (n = 7), and not asthmatic (n = 55). sGaw and FEF_{25 ? 75} decreases from the negative MCT could not predict asthma; however, decreases in FEV₁ were associated with future asthma occurrence (sGaw p = 0.21, FEF25-75 p = 0.07, FEV₁ p = 0.0009). Forty-three percent of the patients who had a 10% to 20% decline in FEV₁ eventually developed asthma. Conclusion. Up to 20% of patients who have symptoms suggestive of asthma but a negative MCT can still develop asthma. Declines in sGaw and FEF_{25 ? 75} in a negative MCT appear to have no clinical significance. A decrease in FEV₁, especially 10% to 20%, is associated with the diagnosis of future asthma.     

Removing individual rats affects indicators of welfare in the remaining group members

The removal of individuals from social groups, e.g. in order to maintain appropriate stocking densities in groups of rapidly growing young laboratory rats, is often necessary. However, such removals may be stressful and few studies have investigated their effects on the behaviour, physiology and welfare of the remaining group members. In this study we investigated this issue for rats housed at different stocking densities by observing behaviour and recording faecal corticosterone metabolite levels both before and after removal. We found that, irrespective of stocking density, the rats remaining in the home cage significantly increased agonistic behaviour, audible vocalization, aggressive grooming, bar-chewing and climbing behaviour following removal of their cage-mates, and that these behavioural changes were associated with a highly significant post-removal increase in their faecal corticosterone metabolite levels. Taking the behavioural and physiological results together, it appears that the removal of individuals from groups of young laboratory rats resulted in social stress, and thus an apparent impairment of welfare.     

Short‐term effects of extracorporeal graft rinse versus circulatory graft rinse in living donor liver transplantation. A prospective randomized controlled trial

Living donor liver transplantation has shorter cold ischemia time, less preservative volume, and lower metabolic load compared to transplantation from deceased donors. We investigated the impact of rinsing the graft contents into the systemic circulation on operative course and postoperative outcomes. Donors had right hepatectomy, and grafts were preserved with cold histidine‐tryptophan‐ketoglutarate solution. On ending portal vein anastomosis, grafts were flushed by patient's portal blood either through incompletely anastomosed hepatic vein (extracorporeal rinse group, EcRg, n = 40) or into systemic circulation (circulatory rinse group, CRg, n = 40). The primary outcome objective was the lowest mean arterial blood pressure within 5 min after portal unclamping as a marker for postreperfusion syndrome (PRS). Secondary objectives included hemodynamics and early graft's and patient's outcomes. Within 5 min postreperfusion, mean arterial blood pressure was significantly lower in the CRg compared to the EcRg, yet this was clinically insignificant. Postoperative graft functions, early biliary and vascular complications, and three‐month survival were comparable in both groups. Rinsing the graft into the circulation increased the incidence of PRS without significant impact on early graft or patient outcome in relatively healthy recipients.     

Creeping posterior synechiae following hyperopic iris-fixated phakic implants

The purpose of this study was to report on the occurrence and management of posterior synechiae (PS) in three hyperopic eyes after iris-fixated anterior chamber phakic IOL implantation. This is a case report of a 55-year-old man and a 55-year-old lady who had undergone iris-fixated anterior chamber phakic IOL implantation to correct hyperopic astigmatism (one eye) and hyperopia (both eyes), respectively. The three eyes developed creeping PS and pigment dispersion within 4–6 weeks of surgery. Synechiolysis and pupil stretching in one eye did not work as the synechiae promptly recurred. Definitive management in the form of removal of the phakic implant and phacoemulsification with lens implant was successful in restoring normal vision in all three eyes. Although implantation of phakic intraocular lenses has been reported to be very effective for the correction of moderate to high degrees of ametropia, this complication can occur in hyperopic eyes. Pigment dispersion has been reported in myopic eyes also, but PS seem to be more an issue with hyperopic eyes. Age of the patient may also be a factor. This information is important in the selection and counselling of patients.     

Metabolomic profiling,biological evaluation of Aspergillus awamori,the river Nile-derived fungus using epigenetic and OSMAC approaches

LC-HRMS-based metabolomics approach was applied to the river Nile-derived fungus Aspergillus awamori after its fermentation on four different media and using four epigenetic modifiers as elicitors. Thereafter, a comprehensive multivariate statistical analysis such as PCA, PLS-DA and OPLS-DA were employed to explain the generated metabolomic data (1587 features). PCA showed that the fungus displayed a unique chemical profile in each medium or elicitor. Additionally, PLS-DA results revealed the upregulated metabolites under each of these conditions. Results indicated that both rice and malt dextrose agar were recognized as the best media in terms of secondary metabolites diversity and showed better profiles than the four applied epigenetic modifiers, of which nicotinamide was the best secondary metabolite elicitor. Testing the antibacterial and cytotoxic effects of all A. awamori-derived extracts revealed that using epigenetic modifiers can induce antimicrobial metabolites against S. aureus and E. coli, whereas using rice, malt dextrose or nicotinamide can induce groups of cytotoxic metabolites. OPLS-DA results assisted in the putative identification of the induced metabolites that could be responsible for these observed inhibitory activities. This study highlighted how powerful the OSMAC approach in maximizing of the chemical diversity of a single organism. Furthermore, it revealed the power of metabolomics in tracing, profiling and categorizing such chemical diversity and even targeting the possible bioactive candidates which require further scaling up studies in the future.

LC-HRMS-based metabolomics approach was applied to the river Nile-derived fungus Aspergillus awamori after its fermentation on four different media and using four epigenetic modifiers as elicitors.