Lipoxins,Resolvins, Protectins,Maresins, and Nitrolipids: Connecting Lipids,Inflammation, and Cardiovascular Disease Risk

Essential fatty acids and their metabolites (γ-linolenic acid [GLA], dihomo-GLA, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid; prostaglandin E₁; prostacyclin [PGI₂]; PGI₃; lipoxins; resolvins; protectins; maresins; and nitrolipids) prevent platelet aggregation, produce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, possess peroxisome proliferator-activated receptor-γ ligand activity, and release nitric oxide. Thus, they lower blood pressure, are anti-arrhythmic and anti-inflammatory in nature, reduce low-density lipoprotein cholesterol, ameliorate the adverse actions of homocysteine, activate telomerase, and have cytoprotective properties—actions that prevent atherosclerosis and cardiovascular disease. Because coronary heart disease (CHD) and atherosclerosis are low-grade systemic inflammatory conditions, it is likely that reduced formation of lipoxins, resolvins, protectins, maresins, and nitrolipids plays a significant role in the pathogenesis of CHD. Hence, development of stable synthetic analogues of lipoxins, resolvins, protectins, and maresins may form a new therapeutic approach to CHD and other low-grade systemic inflammatory conditions.     

Correlations between lipid levels and age, gender, glycemia, obesity, diabetes, and smoking

A low level of high-density lipoprotein cholesterol (HDL-C) is an important cardiovascular risk factor. Dietary measures and pharmacological agents are often not sufficient to reach the HDL-C target level of 40 mg/dl in patients with low baseline HDL-C. This study assesses the association between lipid levels and age, gender, body mass index (BMI), glycemia, diabetes and smoking and focuses on the parameters influencing HDL-C. In the town of Lede (Belgium) all patients aged between 45 and 64 years were invited during 1999 for a free of charge health check-up and blood test. Blood pressure, weight, length and smoking habits were recorded. Serum levels for glycemia and lipoproteins were determined. In total, 629 subjects attended for the check-up. In a logistic regression analysis age above 50 years was correlated with low HDL-C (OR = 2.27 CI = 1.10-4.68). Male gender was correlated with low HDL-C (OR = 3.85 CI = 1.77-8.43) and with high triglycerides (TG) (OR = 1.94 CI = 1.14-3.30). From the level of 90 mg/dl glycemia was correlated with low HDL-C (OR = 2.56 CI = 1.02-6.39) and high TG (OR = 2.12 CI = 1.16-4.06). Obesity was correlated with low HDL-C (OR = 2.36 CI = 1.18-4.71) and high TG (OR = 2.17 CI = 1.88-5.23). This study provides some evidence to sharpen the target levels for glycemia and BMI among patients with low HDL-C and high TG. For these patients, the target glycemia should be around 90 mg/dl and BMI around 25 kg/m2. Physical activity and diet are also important in the achievement of these target levels.     

Cardiovascular,diabetes, and cancer strips: evidences,mechanisms, and classifications

Objectives

To report and name firstly that there are cardiovascular disease (CVD), diabetes mellitus (DM) and cancers (CDC) strips; and disclose their mechanisms, classifications, and clinical significances.

Study design

Narrative and systematic review study and interpretive analysis.

Methods

Data sources and study selection: to collect and present related evidences on CDC strips from evidence-based, open-access, both Chinese- and English-language literatures in recent 10 years on clinical trials from PubMed according to keywords “CVD, DM and cancers” as well as authors’ extensive clinical experience with the treatment of more than fifty thousands of patients with CVD, diabetes and cancers over the past decades, and analyze their related mechanisms and categories which based on authors’ previous works. Data extraction: data were mainly extracted from 48 articles which are listed in the reference section of this review. Qualitative, quantitative and mixed data were included, narratively and systematically reviewed.

Results

With several conceptual and technical breakthrough, authors present related evidences on CDC strips, these are, CVD and DM, DM and cancers, cancers and CVD linked, respectively; And “Bad SEED” +/– “bad soil” theory or doctrine may explain this phenomenon due to “internal environmental injure, abnormal or unbalance” in human body resulting from the role of risk factors (RFs) related multi-pathways and multi-targets, which including organ & tissue (e.g., vascular-specific), cell and gene-based mechanisms. Their classifications include main strips/type B, and Branches/type A as showed by tables and figures in this article.

Conclusions

There are CDC strips and related mechanisms and classifications. CDC strips may help us to understand, prevent, and control related common non-communicable diseases (NCDs) as well as these high risk strips.     

Trust,benefit, satisfaction,and burden

BACKGROUND: Community-based participatory research (CBPR) approaches that actively engage communities in a study are assumed to lead to relevant findings, trusting relationships, and greater satisfaction with the research process. OBJECTIVE: To examine community members' perceptions of trust, benefit, satisfaction, and burden associated with their participation. DESIGN, SETTING, AND PARTICIPANTS: A randomized controlled trial tested a cancer prevention intervention in members of African-American churches. Data were collected at baseline and 1-year follow-up. MEASUREMENTS: Subscales measured perception of trust in the research project and the project team, benefit from involvement with the project, satisfaction with the project and the team, and perception of burden associated with participation. MAIN RESULTS: Overall, we found high levels of trust, perceived benefit, and satisfaction, and low perceived burden among community members in Partnership to Reach African Americans to Increase Smart Eating. In bivariate analyses, participants in the intervention group reported more perceived benefit and trust (P <.05). Participants in smaller churches reported more benefit, satisfaction and trust, while participants from churches without recent health activities perceived greater benefit, greater satisfaction, and lower burden with the project and the team (P <.05). Participants whose pastors had less educational attainment noted higher benefit and satisfaction; those whose pastors were making personal lifestyle changes noted higher benefit and satisfaction, but also reported higher burden (P <.05). CONCLUSIONS: A randomized clinical trial designed with a CBPR approach was associated with high levels of trust and a perceived benefit of satisfaction with the research process. Understanding variations in responses to a research partnership will be helpful in guiding the design and implementation of future CBPR efforts.     

Syphilis, neurosyphilis, penicillin, and AIDS

Early neurosyphilis, characterized by meningitis, cranial nerve abnormalities, and cerebrospinal accidents, was first described in patients with syphilis who received inadequate courses of arsphenamine. Although more effective, penicillin at conventional doses does not yield treponemacidal levels in the central nervous system and probably does not eradicate the infecting organisms, suggesting that it works synergistically with the host's immune response in preventing neurosyphilis. Neurosyphilis after penicillin therapy was almost unheard of in the United States until it began to appear in human immunodeficiency virus (HIV)-infected patients. Numerous cases of syphilitic meningitis, cranial nerve abnormalities, and strokes have been reported in the past decade; about one-half of reported patients had received penicillin therapy, often within the previous 6 months. Thus, more intensive diagnostic evaluation, perhaps including routine cerebrospinal fluid analysis, more intensive therapy, for example with at least three doses of benzathine penicillin, and far more rigorous follow-up are indicated in HIV-infected subjects with syphilis. Since the efficacy of conventional therapy is now uncertain, novel approaches to treatment deserve systematic evaluation.     

Infection, inflammation, height, and longevity

Using historical data from cohorts born before the 20th century in four northern European countries, we show that increasing longevity and declining mortality in the elderly occurred among the same birth cohorts that experienced a reduction in mortality at younger ages. Concurrently, these cohorts also experienced increasing adult height. We hypothesize that both the decline in old-age mortality and the increase in height were promoted by the reduced burden of infections and inflammation. Thus, early growth and cardiovascular diseases of old age may share infectious and inflammatory causes rooted in the external environment.     

Lifestyle factors and stroke risk: Exercise, alcohol, diet, obesity, smoking, drug use, and stress

Various lifestyle factors have been associated with increasing the risk of stroke. These include lack of exercise, alcohol, diet, obesity, smoking, drug use, and stress. Guidelines endorsed by the Centers for Disease Control and Prevention and the National Institutes of Health recommend that Americans should exercise for at least 30 minutes of moderately intense physical activity on most, and preferably all, days of the week. Recent epidemiologic studies have shown a U-shaped curve for alcohol consumption and coronary heart disease mortality, with low-to-moderate alcohol consumption associated with lower overall mortality. High daily dietary intake of fat is associated with obesity and may act as an independent risk factor or may affect other stroke risk factors such as hypertension, diabetes, hyperlipidemia, and cardiac disease. Homocysteine is another important dietary component associated with stroke risk, while other dietary stroke risk factors are thought to be mediated through the daily intake of several vitamins and antioxidants. Smoking, especially current smoking, is a crucial and extremely modifiable independent determinant of stroke. Despite the obstacles to the modification of lifestyle factors, health professionals should be encouraged to continue to identify such factors and help improve our ability to prevent stroke.     

Hemagglutinin Stability and Its Impact on Influenza A Virus Infectivity,Pathogenicity, and Transmissibility in Avians,Mice, Swine,Seals, Ferrets,and Humans

Genetically diverse influenza A viruses (IAVs) circulate in wild aquatic birds. From this reservoir, IAVs sporadically cause outbreaks, epidemics, and pandemics in wild and domestic avians, wild land and sea mammals, horses, canines, felines, swine, humans, and other species. One molecular trait shown to modulate IAV host range is the stability of the hemagglutinin (HA) surface glycoprotein. The HA protein is the major antigen and during virus entry, this trimeric envelope glycoprotein binds sialic acid-containing receptors before being triggered by endosomal low pH to undergo irreversible structural changes that cause membrane fusion. The HA proteins from different IAV isolates can vary in the pH at which HA protein structural changes are triggered, the protein causes membrane fusion, or outside the cell the virion becomes inactivated. HA activation pH values generally range from pH 4.8 to 6.2. Human-adapted HA proteins tend to have relatively stable HA proteins activated at pH 5.5 or below. Here, studies are reviewed that report HA stability values and investigate the biological impact of variations in HA stability on replication, pathogenicity, and transmissibility in experimental animal models. Overall, a stabilized HA protein appears to be necessary for human pandemic potential and should be considered when assessing human pandemic risk.     

Alcohol, age, and piloting: judgement, mood, and actual performance.

We have previously described acute and carry-over effects of alcohol on young and older pilots' performance. In the present paper we report the effects of alcohol and age on self-assessment of performance and mood in the same study. Young and older pilots flew in a simulator during an alcohol and placebo condition. In the alcohol condition, they flew after reaching .04 g/dL (.04%) BAL, after .10% BAL, and then 2, 4, 8, 24, and 48 h after .10% BAL (they flew at the same times in the placebo condition). They rated confidence in ability to fly, mood, alertness, and intoxication before each flight, and perceived workload and performance after each flight. As reported in Morrow et al., alcohol had both acute and carry-over effects for 8 h on actual flight performance, with greater acute impairment for older pilots. The present study reports that these older pilots tended to be more aware than the young pilots of acute and carry-over alcohol impairment out to 4 h. By 8 h, however, all pilots were unaware of impairment. Alcohol also had a biphasic effect on mood, which increased on the ascending limb and decreased on the descending limb of the BAL curve.     

Environmental hazards, hot, cold, altitude, and sun

There has been an increase in both recreational and adventure travel to extreme environments. Humans can successfully acclimatize to and perform reasonably well in extreme environments, provided that sufficient time is given for acclimatization (where possible) and that they use appropriate behavior. This is aided by a knowledge of the problems likely to be encountered and their prevention, recognition, and treatment.     

Lumbar spine radiographic features and demographic,clinical, and radiographic knee,hip, and hand osteoarthritis

Objective

To determine the prevalence of lumbar spine individual radiographic features (IRFs) of disc space narrowing (DSN), osteophytes (OST), and facet joint osteoarthritis (FOA); to describe the frequencies of demographic, clinical, and radiographic knee, hip, and hand osteoarthritis (OA) across lumbar spine IRFs; and to determine factors associated with lumbar spine IRFs.

Methods

We conducted a cross‐sectional study of 840 participants enrolled in the Johnston County Osteoarthritis Project (2003–2004). Sample‐based prevalence estimates were generated for each lumbar spine IRF. The associations between lumbar spine IRFs and demographic, clinical, and peripheral joint OA were determined with logistic regression models.

Results

Sample‐based prevalence estimates were similar for DSN (57.6%) and FOA (57.9%) but higher for OST (88.1%), with significant differences across race and sex. Hand and knee OA frequencies increased across IRFs, whereas the effect was absent for hip OA. African Americans had lower odds of FOA (adjusted odds ratio [OR_adj] 0.45 [95% confidence interval (95% CI) 0.32–0.62]), while there was no racial association with DSN and OST. Low back symptoms were associated with DSN (OR_adj 1.37 [95% CI 1.04–1.80]) but not OST or FOA. Knee OA was associated with OST (OR_adj 1.62 [95% CI 1.16–2.27]) and FOA (OR_adj 1.69 [95% CI 1.15–2.49]) but not DSN. Hand OA was associated with FOA (OR_adj 1.67 [95% CI 1.20–2.28]) but not with DSN or OST. No associations were found with hip OA.

Conclusion

These findings underscore the importance of analyzing lumbar spine IRFs separately as the associations with demographic, clinical, and radiographic knee, hip, and hand OA differ widely.     

Obesity, bariatric surgery, and iron deficiency: true, true, true and related

Morbid obesity is a health problem that has been shown to be refractory to diet, exercise, and medical treatment. Surgeries designed to promote weight loss, termed bariatric surgery and typically involving a gastric bypass procedure, have recently been implemented to treat obesity with high success rates. However, long-term sequelae can result in micronutrient deficiencies. This review will focus on iron deficiency and its association with obesity and bariatric surgery. Iron deficiency develops after gastric bypass for several reasons including intolerance for red meat, diminished gastric acid secretion, and exclusion of the duodenum from the alimentary tract. Menstruating women, pregnant women, and adolescents may be particularly predisposed toward developing iron deficiency and microcytic anemias after bypass surgery. Preoperative assessment of patients should include a complete hematological work-up, including measurement of iron stores. Postoperatively, oral iron prophylaxis and vitamin C in addition to a multivitamin should be prescribed for bypass patients, especially for vulnerable populations. Once iron deficiency has developed, it may prove refractory to oral treatment, and require parenteral iron, blood transfusions, or surgical interventions. Bariatric surgery patients require lifelong follow-up of hematological and iron parameters since iron deficiency and anemia may develop years after surgery.     

Pandemic preparedness: pigs, poultry, and people versus plans, products, and practice

Influenza pandemic preparedness planning is critical for reducing human suffering and negative effects on the economy and society. The Centers for Disease Control and Prevention (CDC) is working to ensure a rapid, efficient, and successful response to an outbreak if, when, and where it appears. The CDC's context for strategic planning is based on experiences with seasonal influenza and what is known about past influenza pandemics. From a public health perspective, pandemic preparedness can be achieved with a plan that builds a network of shared responsibility from the local to the global level, with a focus on saving lives with vaccines, antiviral drugs, medical supplies, containment, and communication.     

Surgery for arrhythmias, myocardial infarction, pericardial disease, cardiac tumors, and trauma, and intraoperative echocardiography

This brief review highlights some of the advances made in selected areas of cardiac surgery over the past year, including surgery for arrhythmias, complications of myocardial infarction, pericardial disease, cardiac tumors, and trauma. In the treatment of arrhythmias, surgery for supraventricular arrhythmias and ventricular tachycardias is discussed, as is the role of the automatic implantable cardioverter-defibrillator in the surgical treatment of ventricular tachycardias. The usefulness of intraoperative echocardiography in evaluating valve disease, valve defects, and the results of surgical repair of atrioventricular septal defects is also discussed. The impact of these exciting developments can be expected to continue over the next several years.     

Vitamins, supplements, herbal medicines, and arrhythmias

Nutritional and herbal supplements may have harmful or beneficial effects on arrhythmias. Potential supplements that may have antiarrhythmic activity include omega-3 polyunsaturated fatty acids (N-3 PUFA), coenzyme Q10, and carnitine. Clinical studies show that N-3 PUFA or fish oil supplementation appears to reduce mortality and sudden death. Coenzyme Q10, used in treatment of heart failure, and carnitine and its derivatives may have beneficial effects on arrhythmias, although clinical studies have been limited. Antioxidant supplements may be beneficial, but large studies with vitamin E have been disappointing in that it does not reduce mortality. Correction of electrolyte disturbances has been long advised and magnesium supplementation has been beneficial in the treatment of torsades de pointes and in some studies after cardiac surgery. However, routine electrolyte supplementation with empiric potassium or magnesium in non-deficient patients has not been convincingly beneficial. Several herbal supplements have also been promoted to have antiarrhythmic activity. However, clinical studies are lacking to support routine use of these herbal medications. In addition, some herbal supplements may cause serious proarrhythmia, and many supplements significantly interact with warfarin and digoxin.     

Effects of functional and surgical castration of white leghorn cockerels, and replacement therapy, on food intake, obesity, reproductive traits, and certain components of blood, liver, muscle, and bone

Basal hypothalamic bilateral electrolytic lesions were placed in White Leghorn cockerels causing functional castration and obesity. Other cockerels were surgically castrated. Determinations were made of the reproductive traits, weight of abdominal adipose tissues, weight and fat content of livers, fat in muscles and bones, hematocrits, plasma calcium, triglycerides, cholesterol, and phospholipid phosphorus before and after injections of chicken pituitaries (CP) into cocks bearing hypothalamic lesions (HL), and before and after injections of testosterone propionate (TP) into surgically castrated (SC) cocks. Treatment of HL cocks with CP partially restored reproductive behavior, but abdominal massage produced only seminal fluid without spermatozoa. The weight of the abdominal adipose tissue was used as a measure of adiposity since it varies directly with total body fat. Adiposity in HL cocks was 2.5 times greater than that of SC cocks. Injections of CP into HL cocks reduced adiposity by 60%. In contrast, injections of TP into SC cocks reduced body fat to normal. Injections with CP into HL cocks reduced moderately the weights of the hypertrophied fatty livers and reduced fat content toward normal, but livers remained abnormal. In surgically castrated cocks, livers remained normal. Functional or surgical castration depressed blood hematocrit values. Injections with TP restored hematocrit values in SC cocks. In contrast, injections of CP into HL cocks were virtually without effect upon the depressed hematocrit values.     

Hyperlipidemia,tissue factor,coagulation, and simvastatin

Hyperlipidemia affects millions of people worldwide and is a major risk factor for cardiovascular disease. People with hyperlipidemia have elevated levels of serum cholesterol and an increased risk of thrombosis. Studies have suggested that oxidized lipoproteins, such as oxidized low-density lipoprotein (oxLDL), contribute to the development of a pro-thrombotic state. In this review, we discuss our recent studies demonstrating a role for hematopoietic cell-derived tissue factor (TF) expression in the activation of coagulation and increased thrombosis associated with hyperlipidemia. In addition, we investigated the effect of simvastatin on TF expression and coagulation. We found that simvastatin reduced leukocyte TF expression, TF⁺ microparticles, and coagulation. These results and earlier studies suggest that the anti-coagulant activity of statins is due, in part, to their ability to reduce monocyte TF expression in patients with cardiovascular disease.     

Idiopathic, immune, infectious, and idiosyncratic neutropenias

In idiopathic and immune neutropenias the susceptibility to infectious agents is highly variable, but the reason why some patients exhibit no undue susceptibility whereas others contract life-threatening infections is poorly understood. An important factor is the efficacy of delivery of neutrophils to the tissues. Recent investigations of the mechanisms for mild to moderate chronic neutropenias have shown the significance of interactions between myelopoiesis and the immune system, as for example, in relation to immunoglobulin aberrations and the cytokine network. Antibody-mediated neutropenias (alloimmune, autoimmune) are now well-characterized diseases. If infections occur, apart from antibiotics, granulocyte colony-stimulating factor (G-CSF) is the treatment of choice, while intravenous or monoclonal immunoglobulins and cyclosporine are reserved for refractory cases.     

Acanthosis Nigricans, insulin action, and hyperandrogenism: clinical, histological, and biochemical findings

Acanthosis nigricans (AN) is a frequent clinical finding in hyperandrogenic women. Its presence has been used to subgroup such women. We performed this study in order to determine the actual histological prevalence of AN and its relationship to sex hormone levels and insulin action. Insulin-mediated glucose disposal was determined by the euglycemic clamp technique, and neck or axillary skin biopsies were graded blind for the presence and severity of AN in lean and obese women with the polycystic ovary syndrome (PCO) and in age- and weight-matched normal ovulatory controls. AN was present on clinical examination in 11 of 13 obese PCO, 3 of 6 lean PCO, 4 of 14 obese normal, and 0 of 4 lean normal women. AN was present on histological examination in 13 of 13 obese PCO, 5 of 6 lean PCO, 13 of 14 obese normal, and 1 of 4 lean normal women. The severity of histological AN was most highly correlated with insulin-mediated glucose disposal (r = -0.61; P less than 0.001) rather than fasting (r = 0.46; P less than 0.05) or glucose-stimulated insulin levels (r = 0.48; P less than 0.01). The only sex steroid correlated with histological AN was dehydroepiandrosterone sulfate (r = 0.46; P less than 0.01). We conclude that 1) clinical skin examination was very insensitive for detecting AN; 2) the best biochemical correlate of histological AN was decreased insulin action, rather than insulin or androgen levels per se; and 3) AN is a very common epiphenomenon of insulin resistance, and its clinical presence should not be used as a criterion for stratifying hyperandrogenic women.     

Apelin, diabetes, and obesity

Apelin is a peptide known as the ligand of the G-protein-coupled receptor APJ. Several active apelin forms exist such as apelin-36, apelin-17, apelin-13, and the pyroglutamated form of apelin-13. Apelin and APJ are expressed in the central nervous system, particularly in the hypothalamus and in many peripheral tissues. Apelin has been shown to be involved in the regulation of cardiovascular and fluid homeostasis, food intake, cell proliferation, and angiogenesis. In addition to be an ubiquitous peptide, apelin is also produced and secreted by adipocytes and thus considered as an adipokine. This has opened a new field of investigation establishing a link between apelin and metabolic disorders (obesity, type 2 diabetes, etc.) which is the focus of the present review. Several studies, but not all, have reported an increase of plasma apelin concentrations in humans and in animal models with different metabolic pathologies. Moreover, important roles for apelin both in glucose and lipid metabolism have been highlighted as well as the associated signaling pathways. Apelin appears as a beneficial adipokine with anti-obesity and anti-diabetic properties and thus as a promising therapeutic target in metabolic disorders.