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BACKGROUND: Excessive body weight is known to cluster with cardiovascular (CV) risk factors, but it is not clear which anthropometric obesity measure provides best independent predictive value of coronary artery disease (CAD). METHODS AND RESULTS: We explored associations between CAD and four different obesity measures (body mass index (BMI), waist circumference, waist/height and waist/height(2)) in a cohort of 16 657 subjects (40.4% men; 20.8% CAD patients), recruited by 700 primary care physicians in 444 Polish cities. 42.8% of subjects were classified as overweight, 31.7% as obese and 39.8% had abdominal obesity. In univariate analyses all obesity measures correlated with CAD (p>0.001), but waist/height(2) was the strongest discriminator between CAD patients and controls. Age-adjusted and sex-adjusted analyses confirmed a graded increase in CAD risk across distributions of all four obesity measures-1 standard deviation (SD) increase in BMI, waist, waist/height and waist/height(2) increased the odds of CAD by 1.23, 1.24, 1.26 and 1.27, respectively (all p<0.001). In models fully adjusted for CV risk factors, waist/height(2) remained the strongest obesity correlate of CAD, being the only independent associate of CAD in men. In a fully adjusted BMI-waist circumference stratified model, sarcopenic obesity (waist > median, BMI < median) and simple obesity (waist and BMI > median) were the strongest independent associates of CAD in men (p = 0.008) and women (p>0.001), respectively. CONCLUSION: This cross-sectional study showed that waist/height(2) may potentially offer a slightly higher predictive value of CAD than BMI or waist circumference and revealed an apparent sexual dimorphism in correlations between obesity measures and CAD. [ABSTRACT FROM AUTHOR]

Obesity has dramatically increased over the past fifty years. In the last decade, it has been noted that augmented body mass, metabolic abnormalities, and the relevant "obese" tumor microenvironment (TME) are connected with signaling molecular networks, which in turn, may contribute to aggressive tumor biology in some patients with breast malignancies. This article presents the associations between obesity, metabolic derangements, inflammatory processes in the adipose tissue or TME, and aggressive behavior of triple-negative breast cancer (TNBC) in African American (AA) women. It also describes some abnormal molecular signaling patterns in the "obese" TME with relevance to TNBC biology. Ethnic disparities in TNBC can be due to a variety of biological features (e.g., genetic mutations and tumor heterogeneity), comorbidities (e.g., cardio-metabolic diseases, including diabetes mellitus), and reproductive factors (e.g., multiparty or short breastfeeding period). Such a constellation of biological variables potentially leads to the association between obesity, metabolic derangements, inflammatory processes in the adipose tissue or TME, and aggressive behavior of TNBC in AA women. Since the TNBC and its TME can display very aggressive behavior, it is crucial that the afflicted AA women make efforts to maintain healthy body weight, "flexible" metabolism, and a well-functioning immune system. Further studies are merited to explore the multi-disciplinary factors that can affect TNBC prevention, management, and outcomes to optimize treatment strategies and survival among AA women., Competing Interests: The author declares that she has no conflicts of interest., (© The Author(s) 2021.)

Epigenetics is the study of inheritable changes in gene expression without changes in the underlying deoxyribonucleic acid (DNA) sequence. The main mechanisms of epigenetic regulation include DNA methylation, modifications in histones, and micro-ribonucleic acids (miRNA). Recent research evidence has shown that environmental and lifestyle factors dynamically interact with the genome, influencing epigenetic changes, from development to the later stages of life. This happens across a spectrum, from physiological to pathological conditions, such as genetic defects, developmental disorders, infectious or inflammatory processes, cancers, mental disorders, and substance abuse. Epigenetic studies have been conducted in various medical disciplines (e.g., oncology, internal medicine or psychiatry), adding valuable insight to standard medical approaches. However, in stomatology, epigenetic research is still in its infancy; thus, this review is aimed at presenting the role of epigenetic mechanisms in diseases of the oral cavity, including periodontal diseases, caries, developmental anomalies, and oral carcinoma. In addition, this paper reveals new insights into epigenetic biomarkers that can be helpful in the detection, early diagnosis, prognosis, and treatment of different oral diseases. Moreover, this review is focused on the possible clinical implications (diagnostic and therapeutic) of epigenetics, in the form of some noninvasive methods that can possibly be used in the future for the screening, work-up, outcome prediction and novel treatments of some dental diseases. Finally, this paper highlights that an epigenetic approach can be useful for designing novel interventions that will improve the management of oral malignancies or developmental abnormalities.

Background: Prevention and treatment of dyslipidemias represent the key issues of Cardiovascular Disease (CVD) prophylaxis. Consequently, the effective management of different types of lipid disorders, including hypertriglyceridemia, should be a priority for the healthcare practitioners (e.g.: cardiology and endocrinology specialists, primary care physicians, dietitians, and pharmacists), who provide medical care, as well as for the patients, who receive this care, and need to be directly engaged in it, in order to improve their outcomes. The aim of this review is to facilitate the translation of current trends in hypertriglyceridemia management into a daily practice. The article focuses on the common causes and consequences of hypertriglyceridemia, and discusses diagnostic evaluation and therapeutic options for patients with high Triglyceride (TG) levels and CVD risk., Conclusion: This review presents the main practice-related strategies, based on the current guidelines for the management of dyslipidemias and CVD risk, according to the European Society of Cardiology (ESC), the European Atherosclerosis Society (EAS), and the American College of Cardiology (ACC)/American Heart Association (AHA), including both non-pharmacological, and pharmacological approaches. It also addresses the beneficial impact of pharmaceutical Care (PC) interventions on clinical outcomes of patients with lipid disorders and CVD risk (in light of Randomized Controlled Trials (RCT) data), and underlines the importance of close cooperation between physicians and pharmacists, who manage such patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Cardiotoxicity of various anticancer therapies, including radiotherapy (RT), can lead to cardiovascular (CV) complications, and their severity depends on many factors, including the site of action, the applied dose, the method of administration, the presence of pre-existing CV diseases, or CV risk factors, the individual patient characteristics, and the current or previous use of antineoplastic therapies. Cardiotoxicity can occur immediately upon administration of the anticancer therapy or it may have a delayed onset (months or years after the treatment). For an oncology treatment team, it is essential that the patients with cancer are in their best cardiac condition before they initiate anticancer therapy, during remission, and after its termination, and thus, a collaboration with cardiologists is of utmost importance. This article reviews cardiotoxicity associated with RT, focusing on patients with breast cancer. In addition, it outlines the main management strategies to assess, monitor, reduce, or possibly prevent RT-induced cardiotoxicity, based on the current research evidence. Medline literature review relating to this subject was performed, using the electronic search for the keywords "radiotherapy" and "cardiotoxicity" on PubMed for inclusion of the previous publications, and further search of reference articles on the detection and management of radiation-related heart disease in patients with breast cancer was conducted.

The naked mole-rat (NMR) Heterocephalus glaber is an exceptionally long-lived rodent, living up to 32 years in captivity. This extended lifespan is accompanied by a phenotype of negligible senescence, a phenomenon of very slow changes in the expected physiological characteristics with age. One of the many consequences of normal aging in mammals is the devastating and progressive loss of skeletal muscle, termed sarcopenia, caused in part by respiratory enzyme dysfunction within the mitochondria of skeletal muscle fibers. Here we report that NMRs avoid sarcopenia for decades. Muscle fiber integrity and mitochondrial ultrastructure are largely maintained in aged animals. While mitochondrial Complex IV expression and activity remains stable, Complex I expression is significantly decreased. We show that aged naked mole-rat skeletal muscle tissue contains some mitochondrial DNA rearrangements, although the common mitochondrial DNA deletions associated with aging in human and other rodent skeletal muscles are not present. Interestingly, NMR skeletal muscle fibers demonstrate a significant increase in mitochondrial DNA copy number. These results have intriguing implications for the role of mitochondria in aging, suggesting Complex IV, but not Complex I, function is maintained in the long-lived naked mole rat, where sarcopenia is avoided and healthy muscle function is maintained for decades., Competing Interests: The authors have no conflict of interests to declare.

Alzheimer's disease (AD) is a multifactorial, progressive neurodegenerative disorder with a poor prognosis, and thus, novel therapies for AD are certainly needed in a growing population of elderly patients or asymptomatic individuals, who are at risk for AD, worldwide. It has been established that some AD biomarkers such as amyloid-beta load in the brain, precede the onset of the disease, by approximately 20 years. Therefore, the therapy to prevent or effectively treat AD has to be initiated before the emergence of symptoms. A goal of this review is to present the results of recent clinical trials on monoclonal antibodies against amyloid beta, used for the treatment of AD and also to address some of the current challenges and emerging strategies to prevent AD. In recent trials, a monoclonal antibody, i.e. solanezumab has shown some beneficial cognitive effects among mild AD patients. Ongoing studies with gantenerumab and crenezumab will examine when exactly the AD treatment, aimed at modifying the disease course has to be started. This review was based on Medline database search for trials on passive anti-AD immunotherapy, for which the main timeframe was set from 2012 to 2015., Competing Interests: There are no conflicts of interest.

Advances in oncologic therapies have allowed many patients with breast cancer to achieve better outcomes and longer survival. However, this progress has been tempered by cardiotoxicity, associated with anticancer therapies, ranging from subclinical abnormalities to irreversible life-threatening complications, such as congestive heart failure or cardiomyopathy. In particular, exposure to chemotherapy (CHT), including anthracyclines and trastuzumab, can lead to cardiac dysfunction with short- or long-term consequences, among patients with breast cancer. The aim of this study is to highlight the potential role of commonly used cardiac medications in the prevention of anthracycline- and trastuzumab-mediated cardiotoxicity, in women with breast cancer, based on evidence from recent clinical trials. This overview is focused on the use of antihypertensive medications, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, outlining their cardioprotective effects in this patient population. In addition, the importance of biomarkers and modern imaging tests, as potential tools for detection and monitoring of cardiac dysfunction, induced by CHT, as well as some practical preventive and therapeutic strategies for cardio-oncology treatment teams, involved in the management of a growing number of women with breast cancer have been outlined. The content of this overview is based on a literature search of PubMed, within the last 5 years, mostly in relevance to the human epidermal growth factor receptor 2-positive patients with breast cancer, treated with anthracycline or trastuzumab therapy (in addition to surgery and/or radiation therapy [RT] regimen).

Rationale: Mechanical ventilation (MV) is associated with adverse effects on the diaphragm, but the cellular basis for this phenomenon, referred to as ventilator-induced diaphragmatic dysfunction (VIDD), is poorly understood., Objectives: To determine whether mitochondrial function and cellular energy status are disrupted in human diaphragms after MV, and the role of mitochondria-derived oxidative stress in the development of VIDD., Methods: Diaphragm and biceps specimens obtained from brain-dead organ donors who underwent MV (15-176 h) and age-matched control subjects were compared regarding mitochondrial enzymatic function, mitochondrial DNA integrity, lipid content, and metabolic gene and protein expression. In addition, diaphragmatic force and oxidative stress after exposure to MV for 6 hours were evaluated in mice under different conditions., Measurements and Main Results: In human MV diaphragms, mitochondrial biogenesis and content were down-regulated, with a more specific defect of respiratory chain cytochrome-c oxidase. Laser capture microdissection of cytochrome-c oxidase-deficient fibers revealed mitochondrial DNA deletions, consistent with damage from oxidative stress. Diaphragmatic lipid accumulation and responses of master cellular metabolic sensors (AMP-activated protein kinase and sirtuins) were consistent with energy substrate excess as a possible stimulus for these changes. In mice, induction of hyperlipidemia worsened diaphragmatic oxidative stress during MV, whereas transgenic overexpression of a mitochondria-localized antioxidant (peroxiredoxin-3) was protective against VIDD., Conclusions: Our data suggest that mitochondrial dysfunction lies at the nexus between oxidative stress and the impaired diaphragmatic contractility that develops during MV. Energy substrate oversupply relative to demand, resulting from diaphragmatic inactivity during MV, could play an important role in this process.

Although denervation has long been implicated in aging muscle, the degree to which it is causes the fiber atrophy seen in aging muscle is unknown. To address this question, we quantified motoneuron soma counts in the lumbar spinal cord using choline acetyl transferase immunhistochemistry and quantified the size of denervated versus innervated muscle fibers in the gastrocnemius muscle using the in situ expression of the denervation-specific sodium channel, Nav₁.₅, in young adult (YA) and senescent (SEN) rats. To gain insights into the mechanisms driving myofiber atrophy, we also examined the myofiber expression of the two primary ubiquitin ligases necessary for muscle atrophy (MAFbx, MuRF1). MN soma number in lumbar spinal cord declined 27% between YA (638±34 MNs×mm⁻¹) and SEN (469±13 MNs×mm⁻¹). Nav₁.₅ positive fibers (1548±70 μm²) were 35% smaller than Nav₁.₅ negative fibers (2367±78 μm²; P<0.05) in SEN muscle, whereas Nav₁.₅ negative fibers in SEN were only 7% smaller than fibers in YA (2553±33 μm²; P<0.05) where no Nav₁.₅ labeling was seen, suggesting denervation is the primary cause of aging myofiber atrophy. Nav₁.₅ positive fibers had higher levels of MAFbx and MuRF1 (P<0.05), consistent with involvement of the proteasome proteolytic pathway in the atrophy of denervated muscle fibers in aging muscle. In summary, our study provides the first quantitative assessment of the contribution of denervation to myofiber atrophy in aging muscle, suggesting it explains the majority of the atrophy we observed. This striking result suggests a renewed focus should be placed on denervation in seeking understanding of the causes of and treatments for aging muscle atrophy.

Aims: To determine: (1) achievement of cholesterol therapy goals in patients receiving lipid-lowering drugs in Polish primary care between the years 2004 and 2006; (2) the characteristics of patients that are associated with attainment of these goals., Design: Cross-sectional study in randomly selected Polish primary care practices., Method: 5248 patients aged over 30 years in 2004 and 5386 patients in 2006, who were taking cholesterol-lowering treatment took part in the study. Physicians recorded demographic and medical history data using a standardized questionnaire, including weight and height, and collected blood samples of patients to determine their cholesterol level., Results: 18.5% of patients attained their optimal goals of therapy (total cholesterol, TC; low-density lipoprotein cholesterol, LDL-C) in 2004 compared to 25.2% in 2006 (p < 0.001). In both 2004 and 2006, more patients achieved their target levels for LDL-C than for TC and statins were the most commonly used medication (85% and 91%, respectively). Male sex, smoking, and higher education were the strongest correlates of the therapeutic outcome. The odds ratio of achieving cholesterol therapy goals in men, non-smokers, and university graduates was estimated at 1.51, 0.70, 1.38 in 2004 and 1.50, 0.73, 1.34 in 2006, respectively., Conclusion: There was a measurable improvement in the effectiveness of hypercholesterolaemia treatment between 2004 and 2006 but the majority of patients remain inadequately treated, with goals not being achieved. There is a need to raise the standard of lipid-lowering management in Poland.

An increase of the body mass often aggravates cardiovascular risk factors. In Poland, over the past 25 years, some epidemiological studies, focused on body mass disorders were conducted. Their results suggest an increase of the prevalence rate of overweight and obesity. The goal of the studies LIPIDOGRAM2004 and LIPIDOGRAM2006 was to assess the prevalence rate of abnormal body mass among adult patients remaining under the care of family physicians in Poland. 17.065 patients in 2004 and 17.152 in 2006, older than 30 years, recruited by 675 study physicians in 444 sites across Poland, were involved into these studies. It was found that approximately 3/4 of the patients included into these studies had BMI > or = 25 kg/m2. Overweight rate was much more prevalent among men than women (48,0% vs. 39,2% in 2004, p<0,0001; 47,4% vs. 39,7% in 2006, p<0,0001). In 2004, obesity was present in above 30% of the participants, including small, but statistically significant difference in the population of men (32,8% vs. 31,2%, p<0,05). In 2006, an increase in the prevalence of obesity in men, compared to women was reported (34,7% vs. 31,6%, p<0,001). Health care actions aimed at decreasing these phenomena would require targeted efforts of family physicians, in collaboration with a multidisciplinary team of specialists.

Objective: The effect leptin on fetal growth in healthy and infected newborns is not well known. This study is aimed at: 1) evaluating serum leptin concentration in full term and preterm, healthy and infected newborns, according to their gender, birth asphyxia, intrauterine and neonatal infections, and 2) assessing the correlation between serum leptin levels and anthropometric parameters among healthy and infected newborns., Materials and Methods: The study involved 146 newborns: 73 full-term and 73 preterm, 86 male and 60 female, 56 healthy and 90 infected, aged from 2nd to 4th day of life. Anthropometric parameters, including: birth weight, length, head and chest circumference, and serum leptin concentration were measured in all the subjects. Intrauterine and neonatal infections were diagnosed by the standard criteria., Results: In this study, it was found that both healthy and infected, but full-term newborns had significantly higher mean leptin concentration than the premature ones (p<0.05). Statistically significant (p<0.05), positive correlations were found between serum leptin level and gestational age, birth weight, head and chest circumference, both in healthy, and in infected newborns., Conclusions: Findings of this study suggest that the serum leptin concentration in full term newborns is higher than in the preterm ones, and in females it is higher than in males, 2) among both healthy and infected newborns, there is a positive, linear correlation between the serum leptin concentration and anthropometric parameters, 3) intrauterine and neonatal infections do not have a significant influence on serum leptin concentration. The role of leptin in fetal growth deserves further research.