COVID-19 and bone health.

A few patients who have recovered from COVID-19 develop persistent or new symptoms that last for weeks or months; this is called "long COVID" or "post-COVID-19 syndrome." Over time, awareness of the short- and long-term consequences of COVID-19 has increased. The pulmonary consequences are now fairly well established, but little is known about the extrapulmonary system of COVID-19, particularly its effects on bones. Current evidence and reports indicate a direct relationship between SARS-CoV-2 infection and bone health, with SARS-CoV-2 having a significant negative effect on bone health. In this review, we analyzed the impact of SARS-CoV-2 infection on bone health and assessed the impact of COVID-19 on the diagnosis and treatment of osteoporosis.

[Investigation and analysis of underground noise in Sichuan coal mines].

Objective: To understand the harm degree of underground noise and provide basis for noise control. Methods: In November 2019, 13 typical coal mines in Sichuan Province were selected as the research objects, and a total of 1203 sites and 609 jobs of noise exposure were investigated. Results: The noise intensity P75 >80 dB (A) was measured. The noise intensity of the inspection place of the air compressor is >86 dB (A) , the noise intensity of the inspection place of the gas drainage and the operation place of the main fan is between 80-85 dB (A) . Conclusion: Besides the harm of dust, noise exposure should also be paid attention to, and the measures of sound absorption and sound insulation should be taken or personal protection should be strengthened.

[Association between a novel regulatory genetic variants and lung cancer risk in Chinese: a two-stage case-control study].

Objective: Regulatory quantitative trait loci (regQTL) theory can help to evaluate the regulation function of single nucleotide polymorphisms (SNPs) on crucial biological signals from a three-dimensional perspective. The aim of this study was to investigate the effect of these regQTL-SNPs on the susceptibility of lung cancer. Methods: Based on the regQTL theory, using the database of identified lung cancer regQTL-SNPs, we screened the SNPs that may function as regQTL in the reported susceptible regions of lung cancer by genome-wide association study(GWAS), and a two-stage case-control study was conducted (screening stage: 2 331 lung cancer cases and 3 077 healthy controls; validation stage: 626 lung cancer cases and 667 healthy controls) to definite the association of related regQTL-SNPs with the susceptibility of lung cancer. Results: A total of 8 regQTL-SNPs were screened in the reported susceptible regions of lung cancer by GWAS. Among which, 3 SNPs were significantly associated with the risk of lung cancer (P<0.05) in the screening stage. Further validation results indicated that the variant T allele of rs6998591 in ADRA1A was significantly associated with increased risk of lung cancer (additive model: OR=1.33, 95%CI:1.01-1.74, P=0.040). In addition, the variant G allele of rs11202916 in ACTA2 was significantly associated with decreased risk of lung cancer (recessive model: OR=0.71, 95%CI:0.52-0.96, P=0.026). Stratified analysis indicated that the variant T allele of rs6998591 significantly increased lung squamous cell carcinoma risk (additive model: OR=1.53, 95%CI: 1.01-2.32, P=0.043), while the variant G allele of rs11202916 significantly decreased lung adenocarcinoma risk (additive model: OR=0.83, 95%CI: 0.69-0.98, P=0.031). Gene-environment interaction analysis indicated that the risk of developing lung cancer increased by 235% in smoking individuals carrying rs6998591 variant T allele compared with those non-smoking individuals carrying no rs6998591 variant T allele(OR=3.35,95%CI:2.10-5.34,P<0.001). Conclusion: There are two regQTL-SNPs that could significantly affect the susceptibility of lung cancer in the GWAS reported susceptible regions of lung cancer.

[Study on the value of serum des-γ-carboxy prothrombin in predicting hepatocellular carcinoma recurrence after liver transplantation].

Objective: To explore the clinical value of serum des-γ-carboxy prothrombin (DCP) in predicting hepatocellular carcinoma recurrence after liver transplantation. Methods: A total of 115 cases with hepatocellular carcinoma who underwent liver transplantation in Zhongshan Hospital Affiliated to Fudan University from October 2016 to December 2018 were retrospectively analyzed. Receiver operating characteristic curve analysis, Mann-Whitney U test, Kaplan-Meier method, Log-Rank test, χ2 test, univariate and multivariate Cox regression analysis and other statistical methods were used to explore the value of DCP in predicting tumor recurrence after liver transplantation and its correlation with clinicopathological characteristics. Results: The preoperative serum DCP level in recurrent population after liver transplantation was significantly higher than that in non-recurrent population (P < 0.001). The optimal cut-off value of preoperative DCP for predicting recurrence was 200mAU/ml with the use of receiver operating characteristic curve. The sensitivity, specificity, Youden's index and the receiver operating characteristic curve was 87.90%, 57.30%, 0.452, and 0.726, respectively. Survival analysis results grouped by this cut-off value showed that patients with preoperative DCP ≥200mAU/ml had a higher probability of recurrence (P < 0.001). Further, subgroup survival analysis showed that patients with preoperative DCP≥200 mAU/ ml had a higher probability of recurrence than other cases of alpha-fetoprotein negative subgroup, cumulative tumor diameter ≤ 9 cm subgroup and Milan criteria subgroup (P < 0.05). Cox regression analysis showed that preoperative DCP≥200 mAU/ ml (P = 0.017) and cumulative tumor diameter > 9 cm (P = 0.014) was an independent risk factor for recurrence after liver transplantation. χ (2) test results showed that preoperative serum DCP level was correlated with gender, serum gamma glutamyltransferase level, serum alpha fetoprotein level, cumulative tumor diameter, vascular invasion, tumor differentiation and liver cancer transplant criteria (P < 0.05). Conclusion: Preoperative serum DCP can be used as a supplement to the existing liver cancer transplant criteria to predict hepatocellular carcinoma recurrence after liver transplantation. In addition, the accurate screening of patients with low risk of HCC recurrence after liver transplantation can improve the prognosis and efficacy of liver transplant patients.

[Focus on the controversial problems of orbital decompression in the treatment of dysthyroid optic neuropathy].

Dysthyroid optic neuropathy (DON) is the most common cause of visual loss in thyroid associated ophthalmopathy, for which steroid pulse therapy and orbital decompression are the common treatments currently. While steroid pulse therapy was recommended as the first-choice for DON, orbital decompression remained as an indispensable therapy although controversies on such treatment still exist. The mechanism, approaches and outcomes of orbital decompression, as well as its advantages and disadvantages over steroid pulse therapy were retrospectively reviewed, and it was suggested that the combination therapy of steroid pulse therapy and surgical decompression might be the better choice for the treatment of DON. (Chin J Ophthalmol, 2018, 54: 488-490).

Synthesis, dual-nonlinear magnetic resonance and microwave absorption properties of nanosheet hierarchical cobalt particles.

In this paper, we report the synthesis of three kinds of novel nanosheet hierarchical cobalt particles by adjusting the [C4H4O6](2-)/Co(2+) ratio through a liquid reduction method. We investigated the electromagnetic properties of the cobalt particles in detail over the microwave frequency range of 1-18 GHz. The results show that the real part of the permittivity decreases and the imaginary part of the permeability increases with an increase in the [C4H4O6](2-)/Co(2+) ratio. The permeability displays two resonance peaks over the frequency range. The cobalt particles with [C4H4O6](2-)/Co(2+) = 6 have a maximum reflection loss of -48.03 dB at 13.61 GHz, and the effective absorption bandwidth (RL ≤ -10 dB) is 6.76 GHz corresponding to a thickness of 1.7 mm. Considering the impedance matching and attenuation based on the electromagnetic parameters, we designed a way to obtain cobalt particles with excellent microwave absorption properties by decreasing the real part of permittivity and increasing the imaginary part of permeability.

Non-vitamin K antagonist oral anticoagulants in cardiovascular disease management: evidence and unanswered questions.

WHAT IS KNOWN AND OBJECTIVE: Anticoagulation is important in the management of cardiovascular disorders; however, traditional anticoagulants such as heparins and vitamin K antagonists (VKAs) have limitations, including parenteral administration with the former and the need for coagulation monitoring and dose adjustments with the latter. Three non-VKA oral anticoagulants (OACs), dabigatran, rivaroxaban and apixaban, are available for the prevention of stroke in patients with atrial fibrillation (AF) and may change clinical practice. This article reviews current knowledge and important unanswered questions on the use of these agents in patients with cardiovascular disease. METHODS: A literature search was performed using PubMed and the search terms dabigatran, rivaroxaban, apixaban, AF and acute coronary syndrome (ACS). Peer-reviewed, published clinical trials, review articles, relevant treatment guidelines and prescribing information documents were identified and reviewed for relevance. RESULTS AND DISCUSSION: Dabigatran is an oral direct thrombin inhibitor; rivaroxaban and apixaban are oral direct Factor Xa inhibitors. These agents have a quicker onset and offset of action, more predictable pharmacokinetic and pharmacodynamic profiles, and fewer drug-drug interactions than VKAs, allowing use of fixed doses. For the prevention of stroke in patients with AF, the non-VKA OACs were either non-inferior or superior to warfarin with similar or improved bleeding profiles, particularly with respect to reductions in intracranial haemorrhage. In patients with ACS receiving dual antiplatelet therapy, the addition of rivaroxaban significantly reduced the rate of death from cardiovascular causes, myocardial infarction or stroke without increasing fatal bleeding, but led to higher rates of major bleeding. Dose reductions with non-VKA OACs are mandated in certain circumstances in patients with AF, such as moderate renal impairment. Contraindications include creatinine clearance <15 mL/min (<30 mL/min for dabigatran in Europe and Canada) and moderate or severe hepatic impairment, but patients can be transitioned to other anticoagulants if appropriate. It is unknown which non-VKA OAC is optimal for stroke prevention in patients with AF, although factors such as co-medications (e.g. dabigatran may be preferred if a patient is taking a co-medication that is a strong cytochrome P450 3A4 inhibitor) and renal function (rivaroxaban and apixaban depend less on renal clearance than dabigatran) will be important for individual patients. Addition of rivaroxaban to antiplatelet therapy for prevention of recurrent events in patients with recent ACS is approved in Europe for patients at the highest risk (with elevated cardiac biomarkers) and must take into account the increased risk of major bleeding. Although routine coagulation monitoring is not required, an understanding of which assays are appropriate for each non-VKA OAC and how they are affected is important. In a bleeding emergency, non-specific prohaemostatic agents are suggested to reverse the action of the non-VKA OACs, but more clinical data are needed. WHAT IS NEW AND CONCLUSION: Non-VKA OACs provide similar or improved efficacy and, on current evidence, improved safety. They provide greater convenience, compared with traditional anticoagulants for the prevention of stroke in patients with AF. Rivaroxaban may be of benefit to selected high-risk patients with ACS. Selection of the most appropriate non-VKA OAC will depend on individual patient factors.

Long-term donor health and its relationship with outcome of allogeneic hematopoietic stem cell transplantation.

Data on long-term follow-up of donors for hematopoietic stem cell transplantation (HSCT) are limited. Donors of 612 adult allogeneic HSCT were studied, at a median of 81 (14-181) months post-HSC donation. Nine donors had severe health problems. Five donors died from aggressive malignancies or terminal illness, at a median of 41 (16-57) months post-donation. Notably, all their recipients had leukemic relapses. In contrast, donors of recipients in remission were all living. This observation might be due to an inherent depressed immunosurveillance in the donors, or selection of donors with suboptimal health for desperate patients with poor risks pre-HSCT.

Nesiritide utilization evaluation in a university teaching hospital.

BACKGROUND AND OBJECTIVES: Nesiritide is a new vasodilator approved for decompensated heart failure (DHF). Compared with nitroglycerin, nesiritide improves haemodynamics and symptoms in the first 3 h of therapy. However, nesiritide is more expensive than nitroglycerin (US$380-1500 daily vs. US$2-5 daily). Since its approval in the US in late 2001, nesiritide use has increased dramatically in our institution. Nesiritide has become a focus of our multidisciplinary drug utilization initiative, aimed at performing a nesiritide utilization evaluation (NUE) and developing a nesiritide usage guideline. METHODS: Medical records of patients who received nesiritide from 1 October 2003 to 31 March 2004 were reviewed. Nesiritide utilization pattern was presented to the initiative group for guideline development. RESULTS: A total of 162 records were reviewed. A 22.6% of inappropriate usage was reported. The most significant inappropriate usage was in patients who received the agent for precardiac valvular surgery optimization, followed by those for diuresis in non-cardiac-related fluid overload states. The median duration of nesiritide therapy was 6 days (range 1-94). The median length of stay (LOS) in our institution was 14 days (National statistics DHF LOS: 5.3 days). Eliminating inappropriate nesiritide usage can lead to a potential of US$141 886 savings per year. CONCLUSION: Based on the results, a 48-h nesiritide restriction policy was implemented. Usage beyond 48 h requires Heart Failure Service approval. Future NUE will evaluate the effectiveness of this policy. The overall management of DHF also needs to be evaluated to improve efficiency of care.

PTPN11 mutations in pediatric patients with acute myeloid leukemia: results from the Children's Cancer Group.

The PTPN11 gene encodes SHP-2, a nonreceptor protein tyrosine phosphatase that relays signals from activated growth factor receptors to p21(ras) (Ras) and other signaling molecules. Somatic PTPN11 mutations are common in patients with juvenile myelomonocytic leukemia (JMML) and have been reported in some other hematologic malignancies. We analyzed specimens from 278 pediatric patients with acute myelogenous leukemia (AML) who were enrolled on Children's Cancer Group trials 2941 and 2961 for PTPN11 mutations. Missense mutations of PTPN11 were detected in 11 (4%) of these samples. None of these patients had mutations in NRAS; however, one patient had evidence of a FLT3 alteration. Four of the patients with PTPN11 mutations (36%) were boys with French-American-British (FAB) morphology M5 AML (P=0.012). Patients with mutations also presented with elevated white blood cell counts. There was no difference in clinical outcome for patients with and without PTPN11 mutations. These characteristics identify a subset of pediatric AML with PTPN11 mutations that share clinical and biologic features with JMML.

Novel peptide inhibitors for Grb2 SH2 domain and their detection by surface plasmon resonance.

One of the critical intracellular signal transduction pathways involves the binding of the Grb2 SH2 domain to the phosphotyrosine (pTyr) motifs on growth factor receptors, such as epidermal growth factor receptor (EGFR) and erbB2, leading to downstream activation of the oncogenic Ras signaling pathway. Therefore, the Grb2 SH2 domain has been chosen as our target for the development of potential anticancer agents. As a continuation of our earlier work, herein we report the design and synthesis of new peptide analogs, and their inhibitory effect on the Grb2 SH2 domain using surface plasmon resonance (SPR) technology. These novel agents do not contain phosphotyrosine or phosphotyrosine mimics. Binding interactions between these peptides and the Grb2 SH2 domain were measured and analyzed using a BIAcore X instrument, which provides detailed information on the real-time detection of the binding interaction. The results of this study should provide important information for the further development of peptides or peptidomimetics with high affinity for the Grb2 SH2 domain.

Embryonic expression of pituitary adenylyl cyclase-activating polypeptide and its selective type I receptor gene in the frog Xenopus laevis neural tube.

The genes encoding pituitary adenylyl cyclase-activating peptide (PACAP) and its selective type I receptor (PAC1) are expressed in the embryonic mouse neural tube, where they may be involved in neurogenesis and neural tube development. We examined here the early expression and potential actions of PACAP and PAC1 in the vertebrate developmental model Xenopus laevis. PACAP and PAC1 mRNAs were first detected by RT-PCR in stage 16-18 embryos (18 hours after fertilization). Two distinct PACAP precursor mRNAs were identified. One encoded both growth hormone-releasing hormone and PACAP, whereas the other encoded only full-length PACAP. Unlike that in the adult, the latter represented the predominant embryonic PACAP mRNA species. In situ hybridization revealed that PACAP and PAC1 mRNAs were restricted to neural cells. PAC1 gene expression was observed mainly in the ventricular zone in the ventral parts of the prosencephalon, mensencephalon, rhombencephalon, and anterior spinal cord. In contrast, PACAP mRNA was localized exclusively in postmitotic cells in the dorsolateral parts of the rhombencephalon and entire spinal cord. Most PACAP mRNA-containing cells were characterized as Rohon-Beard neurons. Exposure of early embryos to UV irradiation, which ventralizes embryos and inhibits neural induction, reduced the expression of PACAP and PAC1 genes. These results suggest that PACAP may be involved in the early development of the embryonic Xenopus neural tube.

Fenoldopam in the prevention of contrast media-induced acute renal failure.

OBJECTIVE: To examine the role of fenoldopam in prevention of contrast media-induced acute renal failure (ARF). DATA SOURCES: A literature search of MEDLINE (from 1966 to October 2000) was performed using the following title search terms: fenoldopam, contrast, and renal failure. STUDY SELECTION: English-language human studies, abstracts, and pertinent animal data were reviewed. DATA SYNTHESIS: Small trials using animals with artificially induced ARF receiving fenoldopam demonstrated improvement in renal function. Preliminary trials in healthy humans have also demonstrated similar results using doses not affecting systemic blood pressure. CONCLUSIONS: Fenoldopam may have a role in the management of ARF induced by contrast dye. However, due to the lack of a large-scale study it cannot be routinely recommended.

Recognition, pathophysiology, and management of acute myocardial infarction.

New insights into the pathophysiology of atherosclerotic plaques leading to acute myocardial infarction (MI) are discussed, along with new diagnostic and treatment strategies. Ischemic heart disease represents a continuum from stable angina to unstable angina to non-Q-wave MI to Q-wave MI. Patients whose angina becomes unstable are classified as having acute coronary syndrome (ACS). It was formerly believed that thrombosis leading to critical occlusion of coronary arteries at the site of atherosclerotic plaque rupture was the common cause of ischemic heart disease. It is now thought that even lesions that do not critically occlude coronary arteries can cause MI. ACS can be caused by the rupture of an unstable atherosclerotic plaque. Vulnerable plaques are usually those causing only mild to moderate stenosis and having a lipid-rich core and a thin, macrophage-dense, collagen-poor fibrous cap. Factors affecting plaque rupture include mechanical injury, circadian rhythm, inflammation, and infection. Progressive thrombosis and vasospasm may follow plaque rupture. The diagnosis of MI starts with the recognition of symptoms of myocardial ischemia that are new or different from the usual pattern. Agents used to prevent or treat plaque rupture and its complications include thrombolytics, antiplatelet agents, antithrombotics, beta-blockers, angiotensin-converting-enzyme (ACE) inhibitors, and nitrates. Once patients survive the acute phase of MI, long-term therapy for prevention of future events begins. Post-MI patients should receive aspirin, beta-blockers, and an ACE inhibitor indefinitely; modification of cardiovascular risk factors is also important. Greater understanding of the pathophysiology of ACS has led to strategies to limit the progression of atherosclerosis and to improve survival and function after an acute event.

Tenecteplase: a review.

BACKGROUND: Certain shortcomings of the available thrombolytic agents have prompted the search for a more fibrin specific fibrinolytic agent with a longer half-life. Such properties would allow bolus administration, possibly leading to faster reperfusion of occluded arteries. OBJECTIVE: This article focuses on the new thrombolytic agent tenecteplase, reviewing its mechanism of action, pharmacokinetic characteristics, clinical efficacy, tolerability, and potential for drug interactions in the management of acute myocardial infarction. METHODS: English-language articles for inclusion in this review were identified through searches of MEDLINE, EMBASE, and International Pharmaceutical Abstracts from 1966 to April 2001. The search terms used included tenecteplase, myocardial infarction, TNK, and TNK-tPA. Abstracts from recent conferences and symposia were also consulted. RESULTS: Tenecteplase is a variant of the native tissue-type plasminogen activator (tPA) molecule that has 14-fold greater fibrin specificity than alteplase, a longer half-life, slower plasma clearance, and 80-fold greater resistance to inhibition by plasminogen activator inhibitor type 1. Its half-life of approximately 18 minutes allows single-bolus administration. In comparative clinical trials, tenecteplase was found to have equivalent efficacy to recombinant tPA (alteplase). The rate of intracranial hemorrhage with tenecteplase was similar to that with alteplase, and tenecteplase was associated with fewer noncerebral complications and less need for blood transfusions. CONCLUSIONS: Tenecteplase appears to be as effective and well tolerated as alteplase in the management of acute myocardial infarction and offers the convenience of single-bolus administration.

Patient-reported adherence to guidelines of the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

OBJECTIVES: To compare antihypertensive drug compliance with treatment guidelines established by the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI), and to identify patient adherence to antihypertensive drugs and factors affecting prescribing patterns. METHODS: Patients filling antihypertensive drug prescriptions in metropolitan New York area pharmacies were enrolled. Pharmacy externs collected patient-reported demographics, medical and drug histories, and blood pressure measurements. Compliance with JNC VI guidelines was assessed. RESULTS: Eight hundred twenty-one patients from 102 pharmacies participated. Blood pressure was controlled in 61% of patients at the time of the study. The most prescribed class of antihypertensive agents was angiotensin-converting enzyme inhibitors, followed by diuretics and beta-blockers. Over the study period, compliance with JNC VI guidelines decreased significantly from 85% to 64% (p<0.05). Thirty-seven percent of patients reported consistent adherence to their antihypertensive regimens. Patients' education level was the only factor found to correlate positively with the appropriateness of antihypertensive agents prescribed. CONCLUSION: Compliance with JNC VI guidelines decreased over time, and patient adherence to drug therapy was suboptimal. Continuing-education efforts to reinforce optimal blood pressure management are necessary.

L-arginine in the management of cardiovascular diseases.

OBJECTIVE: To examine the role of L-arginine in the management of cardiovascular diseases. DATA SOURCES: A MEDLINE search (1966-April 2000) of review articles, using the search terms arginine, nitric oxide, and cardiovascular diseases, was conducted. After reviewing these articles, primary studies using the search terms arginine, hypercholesterolemia, hypertension, diabetes, smoking, ischemic heart disease, and heart failure were reviewed. STUDY SELECTION: English-language human studies were selected and evaluated based on quality of review. DATA SYNTHESIS: Small-scale studies have demonstrated that intravenous L-arginine augments endothelial function by enhancing vasodilation and reducing monocyte adhesion. Oral supplementation demonstrated similar effects as well as improvement of exercise ability in patients with cardiovascular diseases. CONCLUSIONS: L-arginine improves the management of multiple cardiovascular diseases. However, most published human studies are small. Before therapy can be routinely recommended, larger, well-designed studies are required to confirm its effect.

New recommendations from the 1999 American College of Cardiology/American Heart Association acute myocardial infarction guidelines.

OBJECTIVE: To review literature relating to significant changes in drug therapy recommendations in the 1999 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for treating patients with acute myocardial infarction (AMI). DATA SOURCES: 1999 ACC/AHA AMI guidelines, English-language clinical trials, reviews, and editorials researching the role of drug therapy and primary angioplasty for AMI that were referenced in the guidelines were included. Additional data published in 2000 or unpublished were also included if relevant to interpretation of the guidelines. STUDY SELECTION: The articles selected influence AMI treatment recommendations. DATA SYNTHESIS: Many clinicians and health systems use the ACC/AHA AMI guidelines to develop treatment plans for AMI patients. This review highlights important changes in AMI drug therapy recommendations by reviewing the results of recent clinical trials. Insights into evolving drug therapy strategies that may impact future guideline development are also described. CONCLUSIONS: Several changes in drug therapy recommendations were included in the 1999 AMI ACC/AHA guidelines. There is emphasis on administering fibrin-specific thrombolytics secondary to enhanced efficacy. Selection between fibrin-specific agents is unclear at this time. Low response rates to thrombolytics have been noted in the elderly, women, patients with heart failure, and those showing left bundle-branch block on the electrocardiogram. These patient groups should be targeted for improved utilization programs. The use of glycoprotein (GP) IIb/IIIa receptor inhibitors in non-ST-segment elevation MI was emphasized. Small trials combining reduced doses of thrombolytics with GP IIb/IIIa receptor inhibitors have shown promise by increasing reperfusion rates without increasing bleeding risk, but firm conclusions cannot be made until the results of larger trials are known. Primary percutaneous coronary intervention (PCI) trials suggest lower mortality rates for primary PCI when compared with thrombolysis alone. However, primary PCI, including coronary angioplasty, is only available at approximately 13% of US hospitals, making thrombolysis the preferred strategy for most patients. Clopidogrel has supplanted ticlopidine as the recommended antiplatelet agent for patients with aspirin allergy or intolerance following reports of a better safety profile. The recommended dose of unfractionated heparin is lower than previously recommended, necessitating a separate nomogram for patients with acute coronary syndromes. Routine use of warfarin, either alone or in combination with aspirin, is not supported by clinical trials; however, warfarin remains a choice for antithrombotic therapy in patients intolerant to aspirin. Beta-adrenergic receptor blockers continue to be recommended, and emphasis is placed on improving rates of early administration (during hospitalization), even in patients with moderate left ventricular dysfunction. New recommendations for drug treatment of post-AMI patients with low high-density lipoprotein cholesterol and/or elevated triglycerides are included, with either niacin or gemfibrozil recommended as an option. Supplementary antioxidants are not recommended for either primary or secondary prevention of AMI, with new data demonstrating lack of efficacy vitamin E in primary prevention. Estrogen replacement therapy or hormonal replacement therapy should not be initiated solely for prevention of cardiovascular disease, but can be continued in cardiovascular patients already taking long-term therapy for other reasons. Bupropion has been added as a new treatment option for smoking cessation. As drug therapy continues to evolve in treating AMI, more frequent updates of therapy guidelines will be necessary.

The solution structure of [d(CGC)r(amamam)d(TTTGCG)]2.

The solution structure and hydration of a DNA.RNA hybrid chimeric duplex [d(CGC)r(amamam)d(TTTGCG)]2 in which the RNA adenines were substituted by 2'-O-methylated riboadenines was determined using two-dimensional NMR, simulated annealing, and restrained molecular dynamics. Only DNA residue 7T in the 2'-OMe-RNA.DNA junction adopted an O4'-endo sugar conformation, while the other DNA residues including 3C in the DNA.2'-OMe-RNA junction, adopted C1'-exo or C2'-endo conformations. The observed NOE intensity of 2'-O-methyl group to H1' proton of 4am at the DNA.2'-OMe-RNA junction is much weaker than those of 5am and 6am. The 2'-O-methyl group of 4am was found to orient towards the minor groove in the trans domain while the 2'-O-methyl groups of 5am and 6am were found to be in the gauche (+) domain. In contrast to the long-lived water molecules found close to the RNA adenine H2 and H1' protons and the methyl group of 7T in the RNA-DNA junction of [d(CGC)r(aaa)d(TTTGCG)]2, there were no long-lived water molecules found in [d(CGC)r(amamam)d(TTTGCG)]2. This is probably due to the hydrophobic enviroment created by the 2'-O-methylated riboadenines in the minor groove or due to the wider minor groove width in the middle of the structure. In addition, the 2'-O-methylation of riboadenines in pure chimeric duplex increses its melting temperature from 48.5 degrees C to 51.9 degrees C. The characteristic structural features and hydration patterns of this chimeric duplex provide a molecular basis for further therapeutic applications of DNA.RNA hybrid and chimeric duplexes with 2'-modified RNA residues.