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Statins reduce cardiovascular morbidity and mortality in primary and secondary prevention. Despite their efficacy, many persons are unable to tolerate statins due to adverse events such as hepatotoxicity and myalgia/myopathy. In the case of most patients, it seems that mild-to-moderate abnormalities in liver and muscle enzymes are not serious adverse effects and do not outweigh the benefits of coronary heart disease risk reduction. The risk for mortality or permanent organ damage ascribed to statin use is very small and limited to cases of myopathy and rhabdomyolysis. Statin-induced muscle-related adverse events comprise a highly heterogeneous clinical disorder with numerous, complex etiologies and a variety of genetic backgrounds. Every patient who presents with statin-related side effects cannot undergo the type of exhaustive molecular characterization that would include all of these mechanisms. Frequently the only solution is to either discontinue statin therapy/reduce the dose or attempt intermittent dosing strategies at a low dose.

Anthracyclines, especially doxorubicin and daunorubicin, are the drugs of first choice in the treatment of patients with hematologic malignancies, soft-tissue sarcomas, and solid tumors. Unfortunately, the use of anthracyclines is limited by their dose-dependent and cumulative cardiotoxicity. The molecular mechanism responsible for anthracycline-induced cardiotoxicity remains poorly understood, although experimental and clinical studies have shown that oxidative stress plays the main role. Hence, antioxidant agents, especially dexrazoxane, and also other drug classes (statins, β-blockers) proved to have a beneficial effect in protecting against anthracycline-induced cardiotoxicity. According to previous clinical trials, the major high-risk factors for anthracycline-induced cardiotoxicity are age, body weight, female gender, radiotherapy, and other diseases such as Down syndrome, familial dilated cardiomyopathy, diabetes and hypertension. Consequently, further studies are needed to elucidate the molecular pathogenesis of anthracycline-induced cardiotoxicity and also to discover new cardioprotective agents against anthracycline-induced cardiotoxicity.

Obesity is the accumulation of abnormal or excessive fat that may interfere with the maintenance of an optimal state of health. The excess of macronutrients in the adipose tissues stimulates them to release inflammatory mediators such as tumor necrosis factor α and interleukin 6, and reduces production of adiponectin, predisposing to a pro-inflammatory state and oxidative stress. The increased level of interleukin 6 stimulates the liver to synthesize and secrete C-reactive protein. As a risk factor, inflammation is an imbedded mechanism of developed cardiovascular diseases including coagulation, atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus. It is also associated with development of non-cardiovascular diseases such as psoriasis, depression, cancer, and renal diseases. On the other hand, a reduced level of adiponectin, a significant predictor of cardiovascular mortality, is associated with impaired fasting glucose, leading to type-2 diabetes development, metabolic abnormalities, coronary artery calcification, and stroke. Finally, managing obesity can help reduce the risks of cardiovascular diseases and poor outcome via inhibiting inflammatory mechanisms.

Vancomycin has been a predominant treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections for decades. However, growing reservations about its efficacy led to an urgent need for new antibiotics effective against MRSA and other drug-resistant Staphylococcus aureus strains. This review covers three new anti-MRSA antibiotics that have been recently approved by the FDA: dalbavancin, oritavancin, and tedizolid. The mechanism of action, indications, antibacterial activity profile, microbial resistance, pharmacokinetics, clinical efficacy, adverse effects, interactions as well as available formulations and administration of each of these new antibiotics are described. Dalbavancin is a once-a-week, two-dose, long-acting intravenous bactericidal lipoglycopeptide antibiotic. Oritavancin, a lipoglycopeptide with bactericidal activity, was developed as a single-dose intravenous treatment for acute bacterial skin and skin-structure infections (ABSSSI), which offers simplifying treatment of infections. Tedizolid is an oxazolidinone-class bacteriostatic once-daily agent, available for intravenous as well as oral use. Increased ability to overcome bacterial resistance is the main therapeutic advantage of the novel agents over existing antibiotics.

Acute heart failure is still characterized by poor prognosis with high mortality. Diagnosis is based on clinical symptoms and hemodynamic measurements. Early coronary revascularization in cardiogenic shock complicating myocardial infarction improves outcome. The further contemporary therapeutic options in the management of acute heart failure are limited to a merely symptomatic effect with relief of dyspnea, reduction of volume overload and improvement of hemodynamic parameters by vasodilators (in hypertension) or inotropic and vasopressor agents (in hypotension). However, so far no medical therapy has been shown to positively affect clinical outcomes of patients with acute heart failure. Early identification of impending circulatory collapse coupled with rapid implementation of mechanical circulatory support may contribute to mortality reduction as a combined concept of the management of acute heart failure.

Renal cell carcinoma is one of the most malignant tumors, affecting men more frequently than women and constituting nearly 90% of all kidney tumors. Chromophobe renal cell carcinoma has been described as a new histological type of renal cell carcinoma. Chromophobe renal cell carcinoma constitutes up to 5% of all cases of kidney cancer. It is characterized by a significant number of deletions in many chromosomes, as well as the loss of entire chromosomes. Chromophobe renal cell carcinoma arises from tubular cells or cells of the macula densa. In contrast to other types of kidney cancer, it occurs with equal frequency in men and women, mostly in the sixth decade of life. It is characterized by a relatively good prognosis and exhibits a low degree of malignancy. Histopathologic diagnosis of ChRCC can be a diagnostic challenge because these tumors may resemble oncocytoma or conventional cancer. Research by Mathers et al. proposed the use of cytokeratin 7 as a marker useful in the differentiation of these changes.

The newer non-vitamin K dependent anticoagulants (NOACs) have provided a new tool in the armamentarium of physicians treating nonvalvular atrial fibrillation and thromboembolism. Slowly, but steadily, there has been an increased preference of NOACs over vitamin K antagonists. However, the major limiting factor and the concern that precluded their use was lack of reversal in emergent situations. With the advent of reversal agents such as idarucizumab, andexanet alfa and PER977, this gap is also being filled. This will further increase the spectrum of usage of NOACs. In this review we present the detailed information on the completed trials on the reversal agents, the ongoinng trials, and their site of action. The reversal agent idarucizumab is FDA approved and readily available. The others are in clinical trials and are soon expected to be available in clinical practice.

On the 60th anniversary of the first successfully performed renal transplantation, we summarize the historical, current and potential future status of kidney transplantation. We discuss three different aspects with a potential significant influence on kidney transplantation progress: the development of surgical techniques, the influence of regenerative medicine and tissue engineering, and changes in immunosuppression. We evaluate the standard open surgical procedures with modern techniques and compare them to less invasive videoscopic as well as robotic techniques. The role of tissue engineering and regenerative medicine as a potential method for future kidney regeneration or replacement and the interesting search for novel solutions in the field of immunosuppression will be discussed. After 60 years since the first successfully performed kidney transplantation, we can conclude that the greatest achievements are associated with the development of surgical techniques and with planned systemic immunosuppression.

In spite of many years of development and implementation of pre-hospital advanced life support programmes, the survival rate of out-of-hospital cardiac arrest (OHCA) used to be very poor. Neurologic injury from cerebral hypoxia is the most common cause of death in patients with OHCA. In the past two decades, post-resuscitation care has developed many new concepts aimed at improving the neurological outcome and survival rate of patients after cardiac arrest. Systematic post-cardiac arrest care after the return of spontaneous circulation, including induced mild therapeutic hypothermia (TH) in selected patients, is aimed at significantly improving rates of long-term neurologically intact survival. This review summarises the history and current knowledge in the field of mild TH after OHCA.

Coronary artery disease is the leading cause of mortality worldwide. Most acute coronary syndromes are caused by a rupture of a vulnerable atherosclerotic plaque which can be characterized by a lipid-rich necrotic core with an overlying thin fibrous cap. Many vulnerable plaques can cause angiographically mild stenoses due to positive remodelling, which is why the extent of coronary artery disease may be seriously underestimated. In recent years, we have witnessed a paradigm shift in interventional cardiology. We no longer focus solely on the degree of stenosis; rather, we seek to determine the true extent of atherosclerotic disease. We seek to identify high-risk plaques for improvement in risk stratification of patients and prevention. Several imaging methods have been developed for this purpose. Intracoronary near-infrared spectroscopy is one of the most promising. Here, we discuss the possible applications of this diagnostic method and provide a comprehensive overview of the current knowledge.

The best mode of undescended testis (UDT) treatment remains controversial. However, knowledge gained from randomized controlled studies and meta-analyses allowed different groups of researchers to set out guidelines on management of patients with UDT. The authors reviewed recent literature and came to the following conclusions: (1) Hormonal treatment is not recommended, considering both the immediate results (only 15–20% of retained testes descend) and the possible long-term adverse effects on spermatogenesis. (2) Surgery is the treatment of choice; orchiopexy is successful in about 95% of UDT, with a low rate of complications (about 1%). (3) Orchiopexy should be performed between 12 and 18 months of age, or at first contact if diagnosed later.

Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies suggest that DME, DR and AMD are inflammatory conditions characterized by a breakdown of the blood-retinal barrier, inflammatory processes and an increase in vascular permeability. Key factors that seem to have a dominant role in DME, DR and AMD are angiotensin II, prostaglandins and the vascular endothelial growth factor and a deficiency of anti-inflammatory bioactive lipids. The imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DME, DR and AMD. This implies that bioactive lipids that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DME, DR and AMD.

Revolutionary progress has recently changed the landscape of chronic lymphocytic leukemia (CLL). Powerful prognostic factors, especially p53 mutation and/or deletion and IGHV mutation status, have refined individual patient prognosis. Purine analogs and monoclonal antibodies paved the way from palliative treatment to chemoimmunotherapy capable of eradication of minimal residual disease and prolongation of survival. Obinutuzumab (GA-101) and ofatumumab have been recently approved for the treatment of comorbid patients. Bendamustine is available for first-line treatment of patients ineligible for fludarabine, cyclophosphamide, and rituximab (FCR). High-dose glucocorticoids combined with rituximab represent a promising option for refractory CLL; ofatumumab is approved for fludarabine- and alemtuzumab-refractory patients. Allogeneic stem cell transplantation is the only curative option but is feasible in a highly selected group of patients only. The novel small molecule inhibitors ibrutinib and idelalisib have been recently approved for relapsed/refractory CLL. This review provides practical advice for diagnosis, prognostication and treatment of CLL.

Behcet's disease (BD) is a multiorgan inflammatory disease of complex and not entirely elucidated etiology, which was originally diagnosed in patients with aphthous stomatitis, genital ulcerations and ocular manifestations. The entity is endemic in countries of Eastern and Central Asia, especially Turkey and Iran, but rarely seen in Central Europe. As there are no specific diagnostic laboratory tests or histopathologic findings which confirm the preliminary diagnosis, the final diagnosis should be based on clinical criteria. Frequently a definitive diagnosis is established within several years or months after the first manifestations appear. The increased number of cases, recently described worldwide also in the Polish population, indicates that the disease could spread out of endemic areas. The aim of this manuscript is to present the clinical picture, diagnosis criteria and therapeutic approaches of this "international disease" which currently is observed not only in emigrants from Asia but also in native Polish citizens.

The ear lobe crease (ELC) has been defined as a deep wrinkle that extends backwards from the tragus to the auricle. It has been proposed that ELC is a predictor of coronary artery disease (CAD). In this review, we consider the possible association between ELC and CAD. Our aim is to systematically address all the relevant evidence in this field. There are many studies that support an association between ELC and CAD. However, other studies did not find such an association. A recent meta-analysis supports the hypothesis that ELC could be a marker of CAD. However, several limitations raise doubts as to whether we should accept this link.

Although Alois Alzheimer described myelin disruption in Alzheimer’s disease (AD) as early as in 1911, his observation has escaped the attention of researchers since that time. Alzheimer’s disease has been mainly considered as a grey matter disorder; nevertheless, recent evidence suggests that myelin impairment may play an important role in AD pathology. Classical neuropathological changes in AD, e.g. the accumulation of aggregated Aβ 42 and the presence of neurofibrillary tangles, are responsible for neuronal loss, but they may also induce death of oligodendrocytes and myelin damage. There is also evidence that myelin pathology may even precede Aβ and tau pathologies in AD. The state of the art does not allow us to determine whether myelin damage is a primary or a secondary injury in AD subjects. The article presents an overview of current knowledge on the role of myelin in AD pathology and its interactions with Aβ and tau pathologies.

Thyrotropin (TSH) is classically known to be regulated by negative feedback from thyroid hormones and stimulated by thyrotropin-releasing hormone (TRH) from the hypothalamus. At the end of the 1990s, studies showed that thyrotroph cells from the pars tuberalis (PT) did not have TRH receptors and their TSH regulation was independent from TRH stimulation. Instead, PT-thyrotroph cells were shown to have melatonin-1 (MT-1) receptors and melatonin secretion from the pineal gland stimulates TSH- subunit formation in PT. Electron microscopy examinations also revealed some important differences between PT and pars distalis (PD) thyrotrophs. PT-TSH also have low bioactivity in the peripheral circulation. Studies showed that they have different glycosylations and PT-TSH forms macro-TSH complexes in the periphery and has a longer half-life. Photoperiodism affects LH levels in animals via decreased melatonin causing increased TSH- subunit expression and induction of deiodinase-2 (DIO-2) in the brain. Mammals need a light stimulus carried into the suprachiasmatic nucleus (which is a circadian clock) and then transferred to the pineal gland to synthesize melatonin, but birds have deep brain receptors and they are stimulated directly by light stimuli to have increased PT-TSH, without the need for melatonin. Photoperiodic regulations via TSH and DIO 2/3 also have a role in appetite, seasonal immune regulation, food intake and nest-making behaviour in animals. Since humans have no clear seasonal breeding period, such studies as recent ‘’domestication locus’’ studies in poultry are interesting. PT-TSH that works like a neurotransmitter in the brain may become an important target for future studies about humans.

The cardiac autonomic nervous system plays an important role in the genesis and maintenance of atrial fibrillation. Although, pulmonary vein isolation is the cornerstone in today’s approach to atrial fibrillation ablation, a considerable proportion of patients will recur with atrial arrhythmias following this procedure, especially in the non-paroxysmal forms. The pulmonary vein isolation indirectly targets and ablate the ganglionated plexi. This might ultimately enhance the efficacy of the procedure, but an optimal ablation strategy and a reliable method to confirm and quantify the efficacy of vagal denervation following the procedure might be necessary, thus leading to significantly better results.

Psoriatic arthritis (PsA) is a seronegative arthropathy with many clinical manifestations, and it may affect nearly a half of patients with psoriasis. PsA should be diagnosed as early as possible to slow down joint damage and progression of disability. To improve the diagnosis of PsA, physicians should look for peripheral inflammatory pain, axial inflammatory pain, dactylitis, and buttock and sciatic pain. In most patients with PsA, pharmacologic treatment with non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and biologic agents is effective. However, when pharmacological treatment fails, patients with PsA may benefit from orthopedic surgery, which can improve both joint function and quality of life. Total hip arthroplasty, total knee arthroplasty, and arthroscopic synovectomy of the knee are the most common surgical procedures offered to patients with PsA. The management of PsA requires the care of a multidisciplinary team, which should include dermatologists, rheumatologists, physiotherapists, and orthopedic surgeons.

Over 260,000 (2013) new oral squamous cell carcinoma (OSCC) cases are reported annually worldwide. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new molecular markers may be of use in prevention, prognosis, and choice of an appropriate therapy. The intracellular molecular signalling pathway of phosphatidyl-inositol-3-kinase is involved in the process of cell growth, differentiation, migration, and survival. The main components of this pathway: PIK3CA (phosphatidylinositol-4,5-bisphosphate-3-kinase catalytic subunit α), PTEN (phosphatase and tensin homologue deleted on chromosome 10), and AKT (serine-threonine kinase) are potential objects of research when introducing new therapeutic agents. The aim of this paper is to evaluate the PIK3CA, PTEN, and AKT gene mutations as prognostic factors in OSCC and to describe their role in aggressive disease progression. This is crucial for oral cancer biology understanding and for indicating which direction new clinical treatments should take.

Resveratrol (3,5,4-trihydroxystilbene) belongs to a family of polyphenolic compounds known as stilbenes, particularly concentrated in grape and red wine. The aim of our review was to critically review the available evidence of resveratrol effects on brain function and its potential impact on therapy. In preclinical models of cognitive decline, resveratrol displays potent antioxidant activity by scavenging free radicals, reducing quinone reductase 2 activity and upregulating endogenous enzymes. Resveratrol also inhibits pro-inflammatory enzyme expression, reduces nuclear factor-B activation and cytokine release. Treatment with resveratrol can affect multiple signaling pathway effectors involved in cell survival, programmed cell death and synaptic plasticity. Direct and/or indirect activation of the deacetylase sirtuins by resveratrol has also been suggested. In humans, clinical evidence derived from randomized clinical trials suggests that resveratrol is able to improve cerebral blood flow, cerebral vasodilator responsiveness to hypercapnia, some cognitive tests, perceived performances, and the A40 plasma and cerebrospinal fluid level.

The role of vitamin D in perinatology is a subject of major interest in current medicine. There is growing evidence about the role of maternal vitamin D levels in pregnancy outcomes. The aim of this review is to summarize the current literature about the role of vitamin D in perinatology. Evidence from this review suggests associations between low levels of maternal vitamin D and higher risk of certain obstetrical complications. Vitamin D has been found to be related to preeclampsia, gestational diabetes mellitus, low birth weight, and preterm birth. The current literature supports vitamin D supplementation in pregnant women, but more high-quality data are necessary. The problem that remains is how to achieve an optimal 25-hydroxyvitamin D level. To determine the real benefits of vitamin D supplementation in pregnancy, we need high-quality trials in larger groups.

Kawasaki disease is an acute systemic vasculitis that was first reported in 1961. Over the last 5 decades multiple papers have been published to further understand this disease. The diagnosis of Kawasaki disease is made based on the clinical findings. Atypical Kawasaki disease includes patients who do not meet all the criteria for diagnosis. The main complication of Kawasaki disease is coronary aneurysm, and the treatment is intravenous immunoglobulin and aspirin. A second dose of immunoglobulin is given if the patient does not improve, and several other treatment options have been proposed over the last few years as second and third line options.

Pathogens can have a negative influence on dendritic cells (DCs), causing their apoptosis, which prevents active presentation of foreign antigens. It results in a state of immunosuppression which makes the body susceptible to secondary infections. Infected immature DCs have lower expression of co-stimulatory and adhesion molecules, reduced ability to secrete cytokines and an inhibited maturation process and are incapable of effective antigen presentation and activation of T-lymphocytes. In some cases, the ability of DCs to undergo rapid apoptosis is important for the body defense, which is probably because of DCs' ability to cross-present and cooperate with other cells. Apoptotic bodies released from the infected DCs are phagocytosed by other DCs, which then stimulate the effector cells and present antigens more efficiently than infected cells. The aim of this article is to review how the DCs respond to viral and bacterial factors and which biochemical mechanisms are responsible for their apoptosis.

Etiological factors of bone metabolism disorders in inflammatory bowel diseases have been the subject of interest of many researchers. One of the questions often raised is vitamin D deficiency. Calcitriol acts on cells, tissues and organs through a vitamin D receptor. The result of this action is the multi-directional effect of vitamin D. The reasons for vitamin D deficiency are: decreased exposure to sunlight, inadequate diet, inflammatory lesions of the intestinal mucosa and post-gastrointestinal resection states. This leads not only to osteomalacia but also to osteoporosis. Of significance may be the effect of vitamin D on the course of the disease itself, through modulation of the inflammatory mechanisms. It is also necessary to pay attention to the role of vitamin D in skeletal pathology in patients with inflammatory bowel diseases and thus take measures aimed at preventing and treating these disorders through the supplementation of vitamin D.

Lack of physical activity, smoking and/or inappropriate diet can contribute to the increase of oxidative stress, in turn affecting the pathophysiology of cardiovascular diseases. Strong anti-oxidant properties of plant polyphenolic compounds might underlie their cardioprotective activity. This paper reviews recent findings on the anti-oxidant activity of plant leaf extracts and emphasizes their effects on blood platelets, leukocytes and endothelial cells - the targets orchestrating the development and progression of cardiovascular diseases. We also review the evidence linking supplementation with plant leaf extracts and the risk factors defining the metabolic syndrome. The data point to the importance of leaves as an alternative source of polyphenolic compounds in the human diet and their role in the prevention of cardiovascular diseases.

There is no consensus on the definition of dysplasia of the hip (DH). Past and present concepts used to describe DH do not form a complete view of the pathology. Moreover, some authors still present the disease as congenital, not developmental. This prompted authors to analyze the evolution of the definition of DH. Based on the biomedical databases 500 articles and books in the field of hip dysplasia were found and analyzed. Fifteen definitions of hip dysplasia met inclusion criteria, subsequently were analyzed and presented in chronological order. The analysis revealed that currently there is no single, universal definition of hip dysplasia in the aspect of morphological, clinical, and radiological studies. Despite the widely-used term of DH, it is described imprecisely and in different ways. Therefore, it is necessary to develop a multidisciplinary definition of this pathology covering all aspects of hip disorders considered valid in modern orthopaedics.

Aspirin-induced asthma (AIA) is a distinct clinical syndrome characterized by severe asthma exacerbations after ingestion of aspirin or other non-steroidal anti-inflammatory drugs. The exact pathomechanism of AIA remains unknown, though ongoing research has shed some light. Recently, more and more attention has been focused on the role of aspirin in the induction of oxidative stress, especially in cancer cell systems. However, it has not excluded the similar action of aspirin in other inflammatory disorders such as asthma. Moreover, increased levels of 8-isoprostanes, reliable biomarkers of oxidative stress in expired breath condensate in steroid-naïve patients with AIA compared to AIA patients treated with steroids and healthy volunteers, has been observed. This review is an attempt to cover aspirin-induced oxidative stress action in AIA and to suggest a possible related pathomechanism.

Fractional flow reserve (FFR) is considered nowadays as the gold standard for invasive assessment of physiologic stenosis significance and an indispensable tool for decision-making in coronary revascularization. Robust studies have shown that FFR is more effective in accurately identifying which lesions should be stented, and revascularization guided by FFR improves the outcome of coronary artery disease in patients. Therefore, FFR has been upgraded to a class A recommendation in current guidelines when the ischemic potential for specific target lesions is controversial. This article reviews the laboratory practice, functional evaluation of FFR as a gold standard and its emerging clinical application. In addition, novel noninvasive technologies of FFR measurement are discussed in depth.

Statins (HMG-CoA reductase inhibitors) are a group of highly efficient pharmacological agents used for reducing blood cholesterol level and prevention/treatment of cardiovascular disease. Adverse reactions during statin treatment affect quite significant numbers of patients (reportedly from 5% to 20%), with more side effects occurring at higher doses. Reduced statin dosing can be achieved by improved bioavailability of statins, which is fairly low due to poor aqueous solubility, low permeability and high molecular weight of some members of the statin family. Moreover, since hepatic cholesterologenesis is a main target of statin action and extrahepatic inhibition of HMG-CoA reductase has no effect on plasma lipids, hepatic bioavailability, in our opinion, becomes a new important modality of statins maximizing their potential effect on the plasma lipid profile and diminishing their extrahepatic toxicity. Therefore efficient delivery systems of statins into hepatocytes need to be developed and introduced. Uses of nano-emulsifying statin delivery systems which may include vectors of intrahepatic transport, in particular lycopene, are discussed. As a proof of concept, some preliminary results revealing the effect of a lycopene-containing nanoformulation of simvastatin (designated as Lyco-Simvastatin) on LDL in mildly hypercholesterolemic patients are shown.

Prostate, bladder and kidney cancers remain the most common cancers of the urinary tract. Despite improved primary prevention, detection and treatment, the incidence of age-related cancers of the urinary tract is likely to rise as a result of global population ageing. An association of diet with prostate, bladder and kidney carcinogenesis is plausible since the majority of metabolites, including carcinogens, are excreted through the urinary tract. Moreover, large regional differences in incidence rates of urologic tumours exist throughout the world. These rates change when people relocate to different geographic areas, which is suggestive of a strong environmental influence. As a result of these observations, numerous studies have been conducted to assess the effects of diet and nutritional status in kidney, bladder and prostate carcinogenesis. Here, we review the literature assessing the effect of diet and nutritional status on urological cancer risk, which has attracted the most interest.

The trigeminocardiac reflex (TCR) has previously been described in the literature as a reflexive response of bradycardia, hypotension, and gastric hypermotility seen upon mechanical stimulation in the distribution of the trigeminal nerve. The diving reflex (DR) in humans is characterized by breath-holding, slowing of the heart rate, reduction of limb blood flow and a gradual rise in the mean arterial blood pressure. Although the two reflexes share many similarities, their relationship and especially their functional purpose in humans have yet to be fully elucidated. In the present review, we have tried to integrate and elaborate these two phenomena into a unified physiological concept. Assuming that the TCR and the DR are closely linked functionally and phylogenetically, we have also highlighted the significance of these reflexes in humans.

Urinary tract infections (UTIs) are common in pregnant women and pose a great therapeutic challenge, since the risk of serious complications in both the mother and her child is high. Pregnancy is a state associated with physiological, structural and functional urinary tract changes which promote ascending infections from the urethra. Unlike the general population, all pregnant women should be screened for bacteriuria with urine culture, and asymptomatic bacteriuria must be treated in every case that is diagnosed, as it is an important risk factor for pyelonephritis in this population. The antibiotic chosen should have a good maternal and fetal safety profile. In this paper, current principles of diagnosis and management of UTI in pregnancy are reviewed, and the main problems and controversies are identified and discussed.

The phenomenon of circulating cell-free DNA (cfDNA) is important for many biomedical disciplines including the field of exercise biochemistry and physiology. It is likely that cfDNA is released into the plasma by apoptosis of endothelial cells and circulating endothelial progenitor cells (EPCs), and/or by NETosis of immune cells induced by strenuous exercise. Increases of cfDNA are described to be a potential hallmark for the overtraining syndrome, and might be related to aseptic vascular inflammation in athletes. Yet, the relevance of systemic inflammation and cfDNA with endothelial dysfunction in athletes still remains unclear. In this review article, we provide a current overview of exercise-induced cfDNA release to the circulation with special emphasis on its relationship with apoptosis and NETosis and the effect of hypoxic physical activity on vascular inflammation in athletes.

SummaryObjectives: To identify and describe the most critical strategic and operational contributors to the successful implementation of clinical information technologies, as deployed within a moderate sized system of U.S. community hospitals.Background and Setting: CHRISTUS Health is a multi-state system comprised of more than 350 services and 60 hospitals with over 9 000 physicians. The Santa Rosa region of CHRISTUS Health, located in greater San Antonio, Texas is comprised of three adult community hospital facilities and one Children’s hospital each with bed capacities of 142–180. Computerized Patient Order Entry (CPOE) was first implemented in 2012 within a complex market environment. The Santa Rosa region has 2 417 credentialed physicians and 263 mid-level allied health professionals.Methods: This report focuses on the seven most valuable strategies deployed by the Health Informatics team in a large four hospital CHRISTUS region to achieve strong CPOE adoption and critical success lessons learned. The findings are placed within the context of the literature describing best practices in health information technology implementation.Results: While the elements described involved discrete de novo process generation to support implementation and operations, collectively they represent the creation of a new customer-centric service culture in our Health Informatics team, which has served as a foundation for ensuring strong clinical information technology adoption beyond CPOE.Conclusion: The seven success factors described are not limited in their value to and impact on CPOE adoption, but generalize to – and can advance success in – varied other clinical information technology implementations across diverse hospitals. A number of these factors are supported by reports in the literature of other institutions’ successful implementations of CPOE and other clinical information technologies, and while not prescriptive to other settings, may be adapted to yield value elsewhere.

Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal survival and growth, serves as a neurotransmitter modulator, and participates in neuronal plasticity, which is essential for learning and memory. It is widely expressed in the CNS, gut and other tissues. BDNF binds to its high affinity receptor TrkB (tyrosine kinase B) and activates signal transduction cascades (IRS1/2, PI3K, Akt), crucial for CREB and CBP production, that encode proteins involved in β cell survival. BDNF and insulin-like growth factor-1 have similar downstream signaling mechanisms incorporating both p-CAMK and MAPK that increase the expression of pro-survival genes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents exhaustion of β cells. Decreased levels of BDNF are associated with neurodegenerative diseases with neuronal loss, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Thus, BDNF may be useful in the prevention and management of several diseases including diabetes mellitus.

Numerous randomized, double-blind, placebo-controlled studies and observational studies have shown that statins reduce mortality and major cardiovascular events in older high-risk persons with hypercholesterolemia. The Heart Protection Study showed that statins reduced mortality and major cardiovascular events in high-risk persons regardless of the initial level of serum lipids, age, or gender. The updated National Cholesterol Education Program III guidelines state that in very high-risk persons, a serum low-density lipoprotein (LDL) cholesterol level of < 70 mg/dl (1.8 mmol/l) is a reasonable clinical strategy for moderately high-risk persons (2 or more risk factors and a 10-year risk for coronary artery disease of 10% to 20%), and the serum LDL cholesterol should be reduced to < 100 mg/dl (2.6 mmol/l). When LDL cholesterol-lowering drug therapy is used to treat high-risk persons or moderately high-risk persons, the serum LDL cholesterol should be reduced by at least 30% to 40%. The serum LDL cholesterol should be decreased to less than 160 mg/dl in persons at low risk for cardiovascular disease. Addition of other lipid-lowering drugs to statin therapy has not been demonstrated to further reduce cardiovascular events and mortality.

Tumor necrosis factor (TNF) is considered a major proinflammatory cytokine, affecting various aspects of the immune reaction. All five TNF inhibitors currently available on the market (i.e., etanercept, infliximab, adalimumab, certolizumab and golimumab) are top sellers, although indicated only in autoimmune diseases, including rheumatoid arthritis, Crohn's disease and psoriasis. This article briefly discusses the background and place for TNF inhibitors in modern therapy. The main safety aspects of TNF inhibitor administration are described in particular, with special consideration of the available meta-analyses. Finally, perspectives on the next-generation TNF inhibitors and their use in the clinic are given.

Exosomes are nano-sized vesicles that facilitate intercellular communications through carrying genetic materials and functional biomolecules. Owing to their unique size and structure, exosomes have emerged as a useful tool to overcome the limitations of siRNA delivery. The use of exosomes as siRNA delivery vehicles lacks certain disadvantages of the existing foreign delivery systems such as viruses, polycationic polymers and liposomes, and introduces several advantages including inherent capacity to pass through biological barriers and escape from phagocytosis by the reticuloendothelial system, as well as being biocompatible, non-toxic, and immunologically inert. Different strategies have been employed to harness exosome-based delivery systems, including surface modification with targeting ligands, and using exosome-display technology, virus-modified exosomes, and exosome-mimetic vesicles. The present review provides a capsule summary of the recent advances and current challenges in the field of exosome-mediated siRNA delivery.

IgG4-related disease is a set of symptoms resulting from a chronic, usually multiple organ inflammatory condition which affects various organs. It consists of lymphoplasmacytic infiltrations with attendant fibrosis and deep vein thrombosis. Frequently observed tissue lesions are accompanied by elevated IgG4 levels in serum. The etiopathogenesis of the lesions is of multifactor character and the clinical manifestation of the disease is highly diverse. The diagnostic process is based on the patient’s medical history, clinical examination and additional tests, including a histopathological examination of the infected organ’s tissues. Almost forty different locations of the disease have been reported, including disorders of the endocrine system. IgG4-related endocrinopathies are quite rare. However, it is likely that the diagnosis is under-reported due to lack of awareness of this clinical entity. Despite increasing interest in the subject, there are not enough reliable studies evaluating the link between IgG4-RD and endocrine disorders.

The current review presents up-to-date knowledge on tuberculosis (TB) in diabetic patients. On the basis of available literature, there is little doubt about the close relationship between these two conditions. Diabetes mellitus in this association may still contribute substantially to the burden of TB and negatively affect control of the latter. Chronic hyperglycemia at least to some extent may alter the clinical manifestation, radiological appearance, treatment outcome and prognosis of TB. Although the pathogenesis is not clear, diabetes may impair both innate and adaptive immune responses to Mycobacterium tuberculosis. Eventually, effective screening and dual management of the diseases have to be addressed both in low- and high-income countries in order to limit the negative effects of the forthcoming global diabetes epidemic.

Evidence from clinical trials repeatedly confirms the association of diabetes with heart failure, independent of hypertension, atherosclerosis, coronary artery disease and valvular heart disease. However, the importance of coexistence of diabetes and heart failure is not universally recognized, despite the fact that it may significantly contribute to morbidity and mortality of the diabetic population. It seems that prevention of heart failure, early diagnosis, and appropriate management could improve the outcome. Unfortunately, the etiology of heart failure in diabetic patients is still to be elucidated. It is multifactorial in nature and several cellular, molecular and metabolic factors are implicated. Additionally, there are still no definite guidelines on either the diagnosis and treatment of heart failure in diabetic patients or on the therapy of diabetes in subjects with heart failure. This review focuses on the pathophysiology, diagnosis, and prevention of heart failure in the diabetic population as well as management of both comorbidities.

Despite centuries of anatomical studies, controversies and contradictions still exist in the literature regarding the definition, anatomical terminology and the limits of the abdominal wall. We conducted a systematic research of books published from 1901 until December 2012 in Google Books. After the index screening, 16 remaining books were further assessed for eligibility. We decided to exclude journals. The aim of the study was to focus on surface landmarks and borders of the abdominal cavity. After this revision of the literature, we propose that the surface landmarks of the abdominal wall should be standardized.

Type 1 diabetes (T1DM) is an autoimmune disease that requires insulin treatment from the time of diagnosis. Its clinical course depends on both genetic and environmental factors, and the lifestyle of a patient modulates their interaction. The evidence about the influence of lifestyle on the course of T1DM is increasing. In this paper, we present evidence on the relationship between lifestyle parameters and diabetes-related outcomes. We discuss the most commonly addressed factors associated with lifestyle, such as physical activity, nutrition and smoking, and those with sparse evidence in T1DM, such as socioeconomic status, sleep duration, psychological stress and illicit drugs intake.

Cardiac tumors are assumed to be a rare entity. Metastases to the heart are more frequent than primary lesions. Sarcomas make up the majority of cardiac malignant neoplasms. Among them angiosarcoma is the most common and associated with the worst prognosis. Malignant fibrous histiocytoma comprises the minority of cardiac sarcomas and has uncertain etiology as well as pathogenesis. Transthoracic echocardiography remains the widely available screening examination for the initial diagnosis of a cardiac tumor. The clinical presentation is non-specific and the diagnosis is established usually at an advanced stage of the disease. Sarcomas spread preferentially through blood due to their immature vessels without endothelial lining. Surgery remains the method of choice for treatment. Radicalness of the excision is still the most valuable prognostic factor. Adjuvant therapy is unlikely to be effective. The management of cardiac sarcomas must be individualized due to their rarity and significant differences in the course of disease.

Surgical carotid endarterectomy (CEA) was long considered the standard approach for the treatment of atherosclerotic carotid artery disease. This was based on results of several randomized trials demonstrating its effectiveness over the best medical therapy. In the past two decades, patients identified high-risk for surgery were offered carotid artery stenting (CAS) as a less invasive option. Despite its initial limitations, CAS has evolved into an elaborate method currently considered to be equivalent and in selected patients even preferable to CEA. However, outcomes of both procedures are highly operator dependent and a simple stratifying method to prioritize CAS, CEA or medical therapy only has not yet been proposed. In addition, recently published randomized trials highlighted the importance of proper patient selection and rigorous training contributing to low absolute rates of (procedural) adverse events. This review discusses the history and evidence for carotid revascularization and briefly presents technical aspects and innovations in CAS.

Acromegaly often involves the presence of different pathologies of the thyroid gland. Long-lasting stimulation of the follicular epithelium by growth hormone (GH) and insulin-like growth factor 1 (IGF-1) can cause disorders in thyroid function, an increase in its mass and the development of goitre. Acromegalic patients present most frequently with non-toxic multinodular goitre. Nodules are more prevalent in patients with active acromegaly. It has been suggested that then thyroid size increases and it can be reduced through treatment with somatostatin analogues. The relationship between thyroid volume and the level of IGF-1 and the duration of the disease is unclear. Each acromegalic patient requires a hormonal and imaging evaluation of the thyroid when the diagnosis is made, and an accurate evaluation during further observation and treatment. Although the data concerning the co-occurrence of acromegaly and thyroid cancer still remain controversial, it is particularly important to diagnose the patient early and to rule out thyroid cancer.

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases worldwide, presenting a great challenge to the public health systems due to high morbidity and mortality, because of frequent micro-/macro-vascular complications. Many treatment options are now available, with different efficacy as well as mechanisms of action to improve deranged glucose metabolism. We review some of the available data on derivatives of meglitinide, namely nateglinide and repaglinide. These two compounds increase insulin secretion by a mechanism similar to the one of sulfonylureas, but with a shorter half-life. Nateglinide and repaglinide, derivatives of meglitinides, have characteristic pharmacodynamic and pharmacokinetic properties that, together with their proposed mechanism of action, make them useful for type 2 diabetes mellitus, especially when used in combination therapy.

There has been enormous progress in antihypertensive therapy over the last few decades. However, the management of arterial hypertension is still insufficient and more efforts are needed to improve both non-pharmacological and pharmacological treatment of this widely prevalent disease. Renin-angiotensin-aldosterone system (RAAS) inhibition is crucial both for blood pressure (BP) control and for prevention of organ damage or its development in patients with hypertension. Angiotensin-converting enzyme inhibitors and/or sartans block RAAS incompletely. Aliskiren is one of the novel drugs that has been introduced to antihypertensive therapy recently. Up to now no trial has confirmed that aliskiren is efficacious in reducing cardiovascular events. Double RAAS blockade with aliskiren was not always safe. This review article presents the current view on the place of aliskiren in the therapy of arterial hypertension.