The 100 most-cited articles in Journal of Clinical Medicine, 2019

Periodontitis is an infection-driven inflammatory disease in which the composition of biofilms plays a significant role. Dental plaque accumulation at the gingival margin initiates an inflammatory response that, in turn, causes microbial alterations and may lead to drastic consequences in the periodontium of susceptible individuals. Chronic inflammation affects the gingiva and can proceed to periodontitis, which characteristically results in irreversible loss of attachment and alveolar bone. Periodontitis appears typically in adult-aged populations, but young individuals can also experience it and its harmful outcome. Advanced disease is the major cause of tooth loss in adults. In addition, periodontitis is associated with many chronic diseases and conditions affecting general health.

Serum visceral proteins such as albumin and prealbumin have traditionally been used as markers of the nutritional status of patients. Prealbumin is nowadays often preferred over albumin due to its shorter half live, reflecting more rapid changes of the nutritional state. However, recent focus has been on an appropriate nutrition-focused physical examination and on the patient's history for diagnosing malnutrition, and the role of inflammation as a risk factor for malnutrition has been more and more recognized. Inflammatory signals are potent inhibitors of visceral protein synthesis, and the use of these proteins as biomarkers of the nutritional status has been debated since they are strongly influenced by inflammation and less so by protein energy stores. The current consensus is that laboratory markers could be used as a complement to a thorough physical examination. Other markers of the nutritional status such as urinary creatinine or 3-methylhistidine as indicators of muscle protein breakdown have not found widespread use. Serum IGF-1 is less influenced by inflammation and falls…

Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation. Endoplasmic reticulum (ER) stress plays an important role in oxidative stress, as it is also a source of ROS. The tight interconnection between both organelles through mitochondrial-associated membranes (MAMs) means that the ROS generated in mitochondria promote ER stress. Therefore, a state of stress and mitochondrial dysfunction are consequences of this vicious cycle. The implication of mitochondria in insulin release and the exposure of pancreatic β-cells to hyperglycemia make them especially susceptible to oxidative stress and mitochondrial dysfunction. In fact, crosstalk between both mechanisms…

Angiogenesis is the process through which novel blood vessels are formed from pre-existing ones and it is involved in both physiological and pathological processes of the body. Furthermore, tumor angiogenesis is a crucial factor associated with tumor growth, progression, and metastasis. In this manner, there has been a great interest in the development of anti-angiogenesis strategies that could inhibit tumor vascularization. Conventional approaches comprise the administration of anti-angiogenic drugs that target and block the activity of proangiogenic factors. However, as their efficacy is still a matter of debate, novel strategies have been focusing on combining anti-angiogenic agents with chemotherapy or immunotherapy. Moreover, nanotechnology has also been investigated for the potential of nanomaterials to target and release anti-angiogenic drugs at specific sites. The aim of this paper is to review the mechanisms involved in angiogenesis and tumor vascularization and provide an overview of the recent trends in anti-angiogenic strategies for cancer therapy.

Malnutrition is an independent risk factor that negatively influences patients' clinical outcomes, quality of life, body function, and autonomy. Early identification of patients at risk of malnutrition or who are malnourished is crucial in order to start a timely and adequate nutritional support. Nutritional risk screening, a simple and rapid first-line tool to detect patients at risk of malnutrition, should be performed systematically in patients at hospital admission. Patients with nutritional risk should subsequently undergo a more detailed nutritional assessment to identify and quantify specific nutritional problems. Such an assessment includes subjective and objective parameters such as medical history, current and past dietary intake (including energy and protein balance), physical examination and anthropometric measurements, functional and mental assessment, quality of life, medications, and laboratory values. Nutritional care plans should be developed in a multidisciplinary approach, and implemented to maintain and improve patients' nutritional condition. Standardized…

Among natural substances widespread in fruits, vegetables, spices, and medicinal plants, flavonoids and organic acids belong to the promising groups of bioactive compounds with strong antioxidant and anti-inflammatory properties. The aim of the present work was to evaluate the antibacterial activity of 13 common flavonoids (flavones, flavonols, flavanones) and 6 organic acids (aliphatic and aromatic acids). The minimal inhibitory concentrations (MICs) of selected plant substances were determined by the micro-dilution method using clinical strains of four species of pathogenic bacteria. All tested compounds showed antimicrobial properties, but their biological activity was moderate or relatively low. Bacterial growth was most strongly inhibited by salicylic acid (MIC = 250–500 μg/mL). These compounds were generally more active against Gram-negative bacteria: Escherichia coli and Pseudomonas aeruginosa than Gram-positive ones: Enterococcus faecalis and Staphylococcus aureus. An analysis of the antibacterial effect of flavone, chrysin, apigenin, and luteolin showed that the presence of…

The increasing application of Artificial Intelligence (AI) in health and medicine has attracted a great deal of research interest in recent decades. This study aims to provide a global and historical picture of research concerning AI in health and medicine. A total of 27,451 papers that were published between 1977 and 2018 (84.6% were dated 2008⁻2018) were retrieved from the Web of Science platform. The descriptive analysis examined the publication volume, and authors and countries collaboration. A global network of authors' keywords and content analysis of related scientific literature highlighted major techniques, including Robotic, Machine learning, Artificial neural network, Artificial intelligence, Natural language process, and their most frequent applications in Clinical Prediction and Treatment. The number of cancer-related publications was the highest, followed by Heart Diseases and Stroke, Vision impairment, Alzheimer's, and Depression. Moreover, the shortage in the research of AI application to some high burden diseases suggests future directions in AI research. This study…

Hypertensive disorders of pregnancy affect up to 10% of pregnancies worldwide, which includes the 3%-5% of all pregnancies complicated by preeclampsia. Preeclampsia is defined as new onset hypertension after 20 weeks' gestation with evidence of maternal organ or uteroplacental dysfunction or proteinuria. Despite its prevalence, the risk factors that have been identified lack accuracy in predicting its onset and preventative therapies only moderately reduce a woman's risk of preeclampsia. Preeclampsia is a major cause of maternal morbidity and is associated with adverse foetal outcomes including intra-uterine growth restriction, preterm birth, placental abruption, foetal distress, and foetal death in utero. At present, national guidelines for foetal surveillance in preeclamptic pregnancies are inconsistent, due to a lack of evidence detailing the most appropriate assessment modalities as well as the timing and frequency at which assessments should be conducted. Current management of the foetus in preeclampsia involves timely delivery and prevention of adverse effects of prematurity…

Fused deposition modeling (FDM) is a rapidly growing three-dimensional (3D) printing technology and has great potential in medicine. Polyether-ether-ketone (PEEK) is a biocompatible high-performance polymer, which is suitable to be used as an orthopedic/dental implant material. However, the mechanical properties and biocompatibility of FDM-printed PEEK and its composites are still not clear. In this study, FDM-printed pure PEEK and carbon fiber reinforced PEEK (CFR-PEEK) composite were successfully fabricated by FDM and characterized by mechanical tests. Moreover, the sample surfaces were modified with polishing and sandblasting methods to analyze the influence of surface roughness and topography on general biocompatibility (cytotoxicity) and cell adhesion. The results indicated that the printed CFR-PEEK samples had significantly higher general mechanical strengths than the printed pure PEEK (even though there was no statistical difference in compressive strength). Both PEEK and CFR-PEEK materials showed good biocompatibility with and without surface modification. Cell densities on…

Background: Despite being recognised that nutritional intervention is essential, nutritional support is not widely accessible to all patients. Given the incidence of nutritional risk and nutrition wasting, and because cachexia management remains a challenge in clinical practice, a multidisciplinary approach with targeted nutrition is vital to improve the quality of care in oncology. Methods: A literature search in PubMed and Cochrane Library was performed from inception until 26 March. The search consisted of terms on: cancer, nutrition, nutritional therapy, malnutrition, cachexia, sarcopenia, survival, nutrients and guidelines. Key words were linked using “OR” as a Boolean function and the results of the four components were combined by utilizing the “AND” Boolean function. Guidelines, clinical trials and observational studies written in English, were selected. Seminal papers were referenced in this article as appropriate. Relevant articles are discussed in this article. Results: Recent literature supports integration of nutrition screening/assessment in cancer care. Body…

Peptic ulcer is a chronic disease affecting up to 10% of the world’s population. The formation of peptic ulcers depends on the presence of gastric juice pH and the decrease in mucosal defenses. Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) infection are the two major factors disrupting the mucosal resistance to injury. Conventional treatments of peptic ulcers, such as proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists, have demonstrated adverse effects, relapses, and various drug interactions. On the other hand, medicinal plants and their chemical compounds are useful in the prevention and treatment of numerous diseases. Hence, this review presents common medicinal plants that may be used for the treatment or prevention of peptic ulcers.

Acne is a highly prevalent inflammatory skin condition involving sebaceous sties. Although it clearly develops from an interplay of multiple factors, the exact cause of acne remains elusive. It is increasingly believed that the interaction between skin microbes and host immunity plays an important role in this disease, with perturbed microbial composition and activity found in acne patients. Cutibacterium acnes (C. acnes; formerly called Propionibacterium acnes) is commonly found in sebum-rich areas and its over-proliferation has long been thought to contribute to the disease. However, information provided by advanced metagenomic sequencing has indicated that the cutaneous microbiota in acne patients and acne-free individuals differ at the virulent-specific lineage level. Acne also has close connections with the gastrointestinal tract, and many argue that the gut microbiota could be involved in the pathogenic process of acne. The emotions of stress (e.g., depression and anxiety), for instance, have been hypothesized to aggravate acne by altering the gut microbiota and increasing…

Candidiasis has increased substantially worldwide over recent decades and is a significant cause of morbidity and mortality, especially among critically ill patients. Diabetes mellitus (DM) is a metabolic disorder that predisposes individuals to fungal infections, including those related to Candida sp., due to a immunosuppressive effect on the patient. This review aims to discuss the latest studies regarding the occurrence of candidiasis on DM patients and the pathophysiology and etiology associated with these co-morbidities. A comprehensive review of the literature was undertaken. PubMed, Scopus, Elsevier's ScienceDirect, and Springer's SpringerLink databases were searched using well-defined search terms. Predefined inclusion and exclusion criteria were applied to classify relevant manuscripts. Results of the review show that DM patients have an increased susceptibility to Candida sp. infections which aggravates in the cases of uncontrolled hyperglycemia. The conclusion is that, for these patients, the hospitalization periods have increased and are commonly associated with the…

Malnutrition is widespread in older people and represents a major geriatric syndrome with multifactorial etiology and severe consequences for health outcomes and quality of life. The aim of the present paper is to describe current approaches and evidence regarding malnutrition treatment and to highlight relevant knowledge gaps that need to be addressed. Recently published guidelines of the European Society for Clinical Nutrition and Metabolism (ESPEN) provide a summary of the available evidence and highlight the wide range of different measures that can be taken-from the identification and elimination of potential causes to enteral and parenteral nutrition-depending on the patient's abilities and needs. However, more than half of the recommendations therein are based on expert consensus because of a lack of evidence, and only three are concern patient-centred outcomes. Future research should further clarify the etiology of malnutrition and identify the most relevant causes in order to prevent malnutrition. Based on limited and partly conflicting evidence and the limitations of…

Mesenchymal stromal/stem cells (MSCs) exist in almost all tissues, possessing the potential to differentiate into specialized cell types and exert immunomodulatory functions. Thus, they have attracted much attention as a promising therapeutic candidate. Recent studies have demonstrated that paracrine signaling is mainly responsible for the involvement of MSCs in the modulation of immune responses and the progression of diseases. Through release of secretome consisting of a diverse range of cytokines, chemokines, and extracellular vesicles (EVs), MSCs convey regulatory messages to recipient immune cells in the microenvironment. In this review, we focus on the recent advances in how MSCs contribute to immunomodulation through the secretion of paracrine factors. The further improved understanding of the molecular mechanism underlying the interactions between MSCs and immune cells highlights the paracrine biology of MSCs in the modulation of the immune microenvironment and promotes the clinical application of MSCs in regenerative medicine and immune diseases.

Cannabidiol (CBD) is ubiquitous in state-based medical cannabis programs and consumer products for complementary health or recreational use. CBD has intrinsic pharmacologic effects and associated adverse drug events (ADEs) along with the potential for pharmacokinetic and pharmacodynamic drug-drug interactions (DDIs). Given CBD use among patients with complex conditions and treatment regimens, as well as its expanded consumer use, awareness of potential safety issues with CBD is needed. Prescribing information for federally approved products containing CBD were reviewed. Data on ADEs and DDIs were extracted and summarized. Nearly one-half of CBD users experienced ADEs, which displayed a general dose-response relationship. Common ADEs include transaminase elevations, sedation, sleep disturbances, infection, and anemia. Given CBD effects on common biological targets implicated in drug metabolism (e.g., CYP3A4/2C19) and excretion (e.g., P-glycoprotein), the potential for DDIs with commonly used medication is high. General clinical recommendations of reducing substrate doses, monitoring…

Alzheimer's disease (AD) is the most prevalent form of dementia. Despite decades of research following several theoretical and clinical lines, all existing treatments for the disorder are purely symptomatic. AD research has traditionally been focused on neuronal and glial dysfunction. Although there is a wealth of evidence pointing to a significant vascular component in the disease, this angle has been relatively poorly explored. In this review, we consider the various aspects of vascular dysfunction in AD, which has a significant impact on brain metabolism and homeostasis and the clearance of β-amyloid and other toxic metabolites. This may potentially precede the onset of the hallmark pathophysiological and cognitive symptoms of the disease. Pathological changes in vessel haemodynamics, angiogenesis, vascular cell function, vascular coverage, blood-brain barrier permeability and immune cell migration may be related to amyloid toxicity, oxidative stress and apolipoprotein E (APOE) genotype. These vascular deficits may in turn contribute to parenchymal amyloid deposition,…

In the last few years, there has been a wave of articles related to behavioral addictions; some of them have a focus on online pornography addiction. However, despite all efforts, we are still unable to profile when engaging in this behavior becomes pathological. Common problems include: sample bias, the search for diagnostic instrumentals, opposing approximations to the matter, and the fact that this entity may be encompassed inside a greater pathology (i.e., sex addiction) that may present itself with very diverse symptomatology. Behavioral addictions form a largely unexplored field of study, and usually exhibit a problematic consumption model: loss of control, impairment, and risky use. Hypersexual disorder fits this model and may be composed of several sexual behaviors, like problematic use of online pornography (POPU). Online pornography use is on the rise, with a potential for addiction considering the "triple A" influence (accessibility, affordability, anonymity). This problematic use might have adverse effects in sexual development and sexual functioning, especially among…

The Prechtl General Movement Assessment (GMA) has become a cornerstone assessment in early identification of cerebral palsy (CP), particularly during the fidgety movement period at 3–5 months of age. Additionally, assessment of motor repertoire, such as antigravity movements and postural patterns, which form the Motor Optimality Score (MOS), may provide insight into an infant’s later motor function. This study aimed to identify early specific markers for ambulation, gross motor function (using the Gross Motor Function Classification System, GMFCS), topography (unilateral, bilateral), and type (spastic, dyskinetic, ataxic, and hypotonic) of CP in a large worldwide cohort of 468 infants. We found that 95% of children with CP did not have fidgety movements, with 100% having non-optimal MOS. GMFCS level was strongly correlated to MOS. An MOS > 14 was most likely associated with GMFCS outcomes I or II, whereas GMFCS outcomes IV or V were hardly ever associated with an MOS > 8. A number of different movement patterns were associated with more severe functional impairment (GMFCS III–V),…

Indirect calorimetry (IC) is considered as the gold standard to determine energy expenditure, by measuring pulmonary gas exchanges. It is a non-invasive technique that allows clinicians to personalize the prescription of nutrition support to the metabolic needs and promote a better clinical outcome. Recent technical developments allow accurate and easy IC measurements in spontaneously breathing patients as well as in those on mechanical ventilation. The implementation of IC in clinical routine should be promoted in order to optimize the cost-benefit balance of nutrition therapy. This review aims at summarizing the latest innovations of IC as well as the clinical indications, benefits, and limitations.

Atopic dermatitis (AD) is a long-standing inflammatory skin disease that is highly prevalent worldwide. Multiple factors contribute to AD, with genetics as well as the environment affecting disease development. Although AD shows signs of skin barrier defect and immunological deviation, the mechanism underlying AD is not well understood, and AD treatment is often very difficult. There is substantial data that AD patients have a disturbed microbial composition and lack microbial diversity in their skin and gut compared to controls, which contributes to disease onset and atopic march. It is not clear whether microbial change in AD is an outcome of barrier defect or the cause of barrier dysfunction and inflammation. However, a cross-talk between commensals and the immune system is now noticed, and their alteration is believed to affect the maturation of innate and adaptive immunity during early life. The novel concept of modifying skin and gut microbiome by applying moisturizers that contain nonpathogenic biomass or probiotic supplementation during early years may be a preventive and…

Clinical studies, as well as in vitro and in vivo experiments have demonstrated that byproducts from joint replacements induce an inflammatory reaction that can result in periprosthetic osteolysis (PPOL) and aseptic loosening (AL). Particle-stimulated macrophages and other cells release cytokines, chemokines, and other pro-inflammatory substances that perpetuate chronic inflammation, induce osteoclastic bone resorption and suppress bone formation. Differentiation, maturation, activation, and survival of osteoclasts at the bone-implant interface are under the control of the receptor activator of nuclear factor kappa-Β ligand (RANKL)-dependent pathways, and the transcription factors like nuclear factor κB (NF-κB) and activator protein-1 (AP-1). Mechanical factors such as prosthetic micromotion and oscillations in fluid pressures also contribute to PPOL. The treatment for progressive PPOL is only surgical. In order to mitigate ongoing loss of host bone, a number of non-operative approaches have been proposed. However, except for the use of bisphosphonates in selected cases, none are…

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group's cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The…

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints. Untreated RA leads to a destruction of joints through the erosion of cartilage and bone. The loss of physical function is the consequence. Early treatment is important to control disease activity and to prevent joint destruction. Nowadays, different classes of drugs with different modes of action are available to control the inflammation and to achieve remission. In this review, we want to discuss differences and similarities of these different drugs.

Ovarian cancers represent the deadliest among gynecologic malignancies and are characterized by a hierarchical structure with cancer stem cells (CSCs) endowed with self-renewal and the capacity to differentiate. The Wnt/β-catenin signaling pathway, known to regulate stemness in a broad spectrum of stem cell niches including the ovary, is thought to play an important role in ovarian cancer. Importantly, Wnt activity was shown to correlate with grade, epithelial to mesenchymal transition, chemotherapy resistance, and poor prognosis in ovarian cancer. This review will discuss the current knowledge of the role of Wnt signaling in ovarian cancer stemness, epithelial to mesenchymal transition (EMT), and therapy resistance. In addition, the alleged role of exosomes in the paracrine activation of Wnt signaling and pre-metastatic niche formation will be reviewed. Finally, novel potential treatment options based on Wnt inhibition will be highlighted.

The American Psychiatric Association (APA) included internet game disorder (IGD) in section III of the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) on the condition that it guaranteed more clinical research and experience. The World Health Organization (WHO) also included Game Disorder (GD) in the 11th final revision of the International Classification of Diseases (ICD-11) and recently recognized it as a diagnosis code. This study aims to compare clinical characteristics and gaming behavior patterns between the IGD diagnosis criteria proposed by the DSM-5 and the GD diagnosis criteria proposed by the ICD-11 based on clinical cohort data (c-CURE: clinic-Cohort for Understanding of internet addiction Rescue factors in Early life) obtained in the Republic of Korea. Psychologists and psychiatrists conducted semi-structured interviews with children/adolescents and their caregivers to identify IGD (Diagnostic Interview for Internet, Game, SNS, etc. Addiction, DIA), and comorbid psychiatric disorders (Kiddie-Schedule for Affective Disorders and…

The effects of an intermittent fasting diet (IFD) in the general population are still controversial. In this study, we aimed to systematically evaluate the effectiveness of an IFD to reduce body mass index and glucose metabolism in the general population without diabetes mellitus. Cochrane, PubMed, and Embase databases were searched to identify randomized controlled trials and controlled clinical trials that compared an IFD with a regular diet or a continuous calorie restriction diet. The effectiveness of an IFD was estimated by the weighted mean difference (WMD) for several variables associated with glucometabolic parameters including body mass index (BMI) and fasting glucose. The pooled mean differences of outcomes were calculated using a random effects model. From 2814 studies identified through a literature search, we finally selected 12 articles (545 participants). Compared with a control diet, an IFD was associated with a significant decline in BMI (WMD, −0.75 kg/m2; 95% CI, −1.44 to −0.06), fasting glucose level (WMD, −4.16 mg/dL; 95% CI, −6.92 to −1.40), and homeostatic…

Photodynamic therapy (PDT) involves the selective sensitization of tissues to light. A major advance in the field occurred when Thomas Dougherty at the Roswell Park Cancer Institute initiated a series of clinical studies that eventually led to FDA approval of the procedure. This report contains a summary of Dougherty's contributions and an assessment of where this has led, along with a summary of implications for future drug development.

Statins are a cornerstone in the pharmacological prevention of cardiovascular disease. Although generally well tolerated, a small subset of patients experience statin-related myotoxicity (SRM). SRM is heterogeneous in presentation; phenotypes include the relatively more common myalgias, infrequent myopathies, and rare rhabdomyolysis. Very rarely, statins induce an anti-HMGCR positive immune-mediated necrotizing myopathy. Diagnosing SRM in clinical practice can be challenging, particularly for mild SRM that is frequently due to alternative aetiologies and the nocebo effect. Nevertheless, SRM can directly harm patients and lead to statin discontinuation/non-adherence, which increases the risk of cardiovascular events. Several factors increase systemic statin exposure and predispose to SRM, including advanced age, concomitant medications, and the nonsynonymous variant, rs4149056, in SLCO1B1, which encodes the hepatic sinusoidal transporter, OATP1B1. Increased exposure of skeletal muscle to statins increases the risk of mitochondrial dysfunction, calcium signalling disruption, reduced…

This review presents an update on the diagnosis and management of acute limb ischemia (ALI), a severe condition associated with high mortality and amputation rates. A comprehensive spectrum of ALI etiology is presented, with highlights on embolism and in situ thrombosis. The steps for emergency diagnosis are described, emphasizing the role of clinical data and imaging, mainly duplex ultrasound, CT angiography and digital substraction angiography. The different therapeutic techniques are presented, ranging from pharmacological (thrombolysis) to interventional (thromboaspiration, mechanical thrombectomy, and stent implantation) techniques to established surgical revascularization (Fogarty thrombembolectomy, by-pass, endarterectomy, patch angioplasty or combinations) and minor or major amputation of necessity. Postprocedural management, reperfusion injury, compartment syndrome and long-term treatment are also updated.

Ecological momentary assessment (EMA) and ecological momentary intervention (EMI) are alternative approaches to retrospective self-reports and face-to-face treatments, and they make it possible to repeatedly assess patients in naturalistic settings and extend psychological support into real life. The increase in smartphone applications and the availability of low-cost wearable biosensors have further improved the potential of EMA and EMI, which, however, have not yet been applied in clinical practice. Here, we conducted a systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to explore the state of the art of technology-based EMA and EMI for major depressive disorder (MDD). A total of 33 articles were included (EMA = 26; EMI = 7). First, we provide a detailed analysis of the included studies from technical (sampling methods, duration, prompts), clinical (fields of application, adherence rates, dropouts, intervention effectiveness), and technological (adopted devices) perspectives. Then, we identify the advantages of…

The purpose of this systematic review is to analyze and summarize the current knowledge regarding the use of yoga to manage and prevent stress and burnout in healthcare workers. In February 2017, a literature search was conducted using the databases Medline (PubMed) and Scopus. Studies that addressed this topic were included. Eleven articles met the inclusion criteria. Seven studies were clinical trials that analyzed yoga interventions and evaluated effectiveness by gauging stress levels, sleep quality and quality of life. A study on Chinese nurses showed statistical improvement in stress levels following a six-month yoga program (χ2 = 16.449; p < 0.001). A population of medical students showed improvement in self-regulation values after an 11-week yoga program (from 3.49 to 3.58; p = 0.04) and in self-compassion values (from 2.88 to 3.25; p = 0.04). Four of the included articles were observational studies: They described the factors that cause stress in the work environment and highlighted that healthcare workers believe it is possible to benefit from improved physical, emotional…

Coagulopathy commonly occurs in sepsis as a critical host response to infection that can progress to disseminated intravascular coagulation (DIC) with an increased mortality. Recent studies have further defined factors responsible for the thromboinflammatory response and intravascular thrombosis, including neutrophil extracellular traps, extracellular vesicles, damage-associated molecular patterns, and endothelial glycocalyx shedding. Diagnosing DIC facilitates sepsis management, and is associated with improved outcomes. Although the International Society on Thrombosis and Haemostasis (ISTH) has proposed criteria for diagnosing overt DIC, these criteria are not suitable for early detection. Accordingly, the ISTH DIC Scientific Standardization Committee has proposed a new category termed "sepsis-induced coagulopathy (SIC)" to facilitate earlier diagnosis of DIC and potentially more rapid interventions in these critically ill patients. Therapy of SIC includes both treatment of the underlying infection and correcting the coagulopathy, with most therapeutic approaches focusing on…

Obesity is one of the main risk factors for type 2 diabetes mellitus (T2DM). It is closely related to metabolic disturbances in the adipose tissue that primarily functions as a fat reservoir. For this reason, adipose tissue is considered as the primary site for initiation and aggravation of obesity and T2DM. As a key endocrine organ, the adipose tissue communicates with other organs, such as the brain, liver, muscle, and pancreas, for the maintenance of energy homeostasis. Two different types of adipose tissues-the white adipose tissue (WAT) and brown adipose tissue (BAT)-secrete bioactive peptides and proteins, known as "adipokines" and "batokines," respectively. Some of them have beneficial anti-inflammatory effects, while others have harmful inflammatory effects. Recently, "exosomal microRNAs (miRNAs)" were identified as novel adipokines, as adipose tissue-derived exosomal miRNAs can affect other organs. In the present review, we discuss the role of adipose-derived secretory factors-adipokines, batokines, and exosomal miRNA-in obesity and T2DM. It will provide new insights into…

Mutations in the protein DJ-1 cause autosomal recessive forms of Parkinson's disease (PD) and oxidized DJ-1 is found in the brains of idiopathic PD individuals. While several functions have been ascribed to DJ-1 (most notably protection from oxidative stress), its contribution to PD pathogenesis is not yet clear. Here we provide an overview of the clinical research to date on DJ-1 and the current state of knowledge regarding DJ-1 characterization in the human brain. The relevance of DJ-1 as a PD biomarker is also discussed, as are studies exploring DJ-1 as a possible therapeutic target for PD and neurodegeneration.

Breast cancer is the most prevalent cancer and primary cause of cancer-related mortality in women. The identification of risk factors can improve prevention of cancer, and obesity and hypercholesterolemia represent potentially modifiable breast cancer risk factors. In the present work, we review the progress to date in research on the potential role of the main cholesterol transporters, low-density and high-density lipoproteins (LDL and HDL), on breast cancer development. Although some studies have failed to find associations between lipoproteins and breast cancer, some large clinical studies have demonstrated a direct association between LDL cholesterol levels and breast cancer risk and an inverse association between HDL cholesterol and breast cancer risk. Research in breast cancer cells and experimental mouse models of breast cancer have demonstrated an important role for cholesterol and its transporters in breast cancer development. Instead of cholesterol, the cholesterol metabolite 27-hydroxycholesterol induces the proliferation of estrogen receptor-positive breast cancer cells…

Atherosclerotic coronary artery disease (CAD) results from build-up of cholesterol-rich plaques in the walls of the coronary arteries and is a leading cause of death. Inflammation is central to atherosclerosis. Uncontrolled inflammation makes coronary plaques "unstable" and vulnerable to rupture or erosion, leading to thrombosis and myocardial infarction (MI). As multiple inflamed plaques often co-exist in the coronary system, patients are at risk of repeated atherothrombotic cardiovascular events after MI, with rates of 10-12% at one year and 18-20% at three years. This is largely because current therapies for CAD, such as lipid-lowering statins, do not adequately control plaque inflammation. New anti-atherosclerotic agents are therefore needed, especially those that better target inflammation. The recent positive results for the anti-interleukin-1-beta (IL-1β) monoclonal antibody, Canakinumab, in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) clinical trial has provided a major stimulant to the field. It highlights that not only is inflammation important from…

Multidrug-resistant (MDR) Klebsiella pneumoniae represents an increasing threat to human health, causing difficult-to-treat infections with a high mortality rate. Since colistin is one of the few treatment options for carbapenem-resistant K. pneumoniae infections, colistin resistance represents a challenge due to the limited range of potentially available effective antimicrobials, including tigecycline, gentamicin, fosfomycin and ceftazidime/avibactam. Moreover, the choice of these antimicrobials depends on their pharmacokinetics/pharmacodynamics properties, the site of infection and the susceptibility profile of the isolated strain, and is sometimes hampered by side effects. This review describes the features of colistin resistance in K. pneumoniae and the characteristics of the currently available antimicrobials for colistin-resistant MDR K. pneumoniae, as well as the characteristics of novel antimicrobial options, such as the soon-to-be commercially available plazomicin and cefiderocol. Finally, we consider the future use of innovative therapeutic strategies in development,…

Sodium-glucose co-transporter 2 inhibitors (iSGLT2) have been linked to a considerable reduction in cardiovascular risk in patients with type 2 diabetes (T2D), but the precise molecular mechanisms are still elusive. We aimed to evaluate the effects of the iSGLT2 empagliflozin on systemic inflammation and its potential antioxidant properties. This is an observational, prospective follow-up study of a cohort of fifteen patients with T2D who received 10 mg/day of empagliflozin according to standard clinical care. Measures at baseline, 12 and 24 weeks were taken. Metabolic and anthropometric parameters were evaluated. Production of mitochondrial superoxide, glutathione content, and glutathione s-reductase and catalase mRNA levels were measured in leukocytes. Serum levels of myeloperoxidase, hs-CRP and IL-10 were determined. In addition to decreased body weight and reduced glucose and HbA1c levels, we observed a reduction in superoxide production in leukocytes of diabetic patients and increased glutathione content, prominently after 24 weeks of empagliflozin treatment. Leukocyte…

Most diagnostic tests for tuberculosis (TB) rely on sputum samples, which are difficult to obtain and have low sensitivity in immunocompromised patients, patients with disseminated TB, and children, delaying treatment initiation. The World Health Organization (WHO) calls for the development of a rapid, biomarker-based, non-sputum test capable of detecting all forms of TB at the point-of-care to enable immediate treatment initiation. Lipoarabinomannan (LAM) is the only WHO-endorsed TB biomarker that can be detected in urine, an easily collected sample. This status update discusses the characteristics of LAM as a biomarker, describes the performance of first-generation urine LAM tests and reasons for slow uptake, and presents considerations for developing the next generation of more sensitive and impactful tests. Next-generation urine LAM tests have the potential to reach adult and pediatric patients regardless of HIV status or site of infection and facilitate global TB control. Implementation and scale-up of existing LAM tests and development of next-generation assays should be…

Both environmental and genetic factors contribute to relative species abundance and metabolic characteristics of the intestinal microbiota. The intestinal microbiota and accompanying microbial metabolites differ substantially in those who are obese or have other metabolic disorders. Accumulating evidence from germ-free mice and antibiotic-treated animal models suggests that altered intestinal gut microbiota contributes significantly to metabolic disorders involving impaired glucose and lipid metabolism. This review will summarize recent findings on potential mechanisms by which the microbiota affects intestinal lipid and lipoprotein metabolism including microbiota dependent changes in bile acid metabolism which affects bile acid signaling by bile acid receptors FXR and TGR5. Microbiota changes also involve altered short chain fatty acid signaling and influence enteroendocrine cell function including GLP-1/GLP-2-producing L-cells which regulate postprandial lipid metabolism.

Electrical impedance tomography (EIT) is a bedside monitoring tool that noninvasively visualizes local ventilation and arguably lung perfusion distribution. This article reviews and discusses both methodological and clinical aspects of thoracic EIT. Initially, investigators addressed the validation of EIT to measure regional ventilation. Current studies focus mainly on its clinical applications to quantify lung collapse, tidal recruitment, and lung overdistension to titrate positive end-expiratory pressure (PEEP) and tidal volume. In addition, EIT may help to detect pneumothorax. Recent studies evaluated EIT as a tool to measure regional lung perfusion. Indicator-free EIT measurements might be sufficient to continuously measure cardiac stroke volume. The use of a contrast agent such as saline might be required to assess regional lung perfusion. As a result, EIT-based monitoring of regional ventilation and lung perfusion may visualize local ventilation and perfusion matching, which can be helpful in the treatment of patients with acute respiratory distress syndrome (ARDS).

The aim of this study was to identify inflammatory mediators of potential clinical relevance in synovial fluid (SF) samples of patients with knee osteoarthritis (OA). Therefore, radiographic OA severity, knee pain and function of 34 OA patients undergoing unicompartmental (UC) and bicompartmental (BC) knee arthroplasty were assessed prior to surgery and SF samples were analyzed for a broad variety of inflammatory mediators, including interleukins (ILs), interferons (IFNs), C-X-C motif ligand chemokines (CXCLs), and growth factors (nerve growth factor; NGF, vascular endothelial growth factor; VEGF, and stem cell growth factor β; SCGF-β) using multiplex assay. Significant differences were observed between the SF levels of different inflammatory markers. When compared to UC OA, significantly higher concentrations of IL-7, IL-8, IL-10, IL-12, IL-13, IFN-γ, VEGF and CXCL1 were detected in BC OA. Correlation analyses revealed significant associations between OA severity and IL-6, IL-8, IFN-γ, SCGF-β, VEGF, CXCL1. Interestingly, increases in both anti- (IL-10, IL-13) and pro-inflammatory…

In early gastric cancer (EGC), tumor invasion depth is an important factor for determining the treatment method. However, as endoscopic ultrasonography has limitations when measuring the exact depth in a clinical setting as endoscopists often depend on gross findings and personal experience. The present study aimed to develop a model optimized for EGC detection and depth prediction, and we investigated factors affecting artificial intelligence (AI) diagnosis. We employed a visual geometry group(VGG)-16 model for the classification of endoscopic images as EGC (T1a or T1b) or non-EGC. To induce the model to activate EGC regions during training, we proposed a novel loss function that simultaneously measured classification and localization errors. We experimented with 11,539 endoscopic images (896 T1a-EGC, 809 T1b-EGC, and 9834 non-EGC). The areas under the curves of receiver operating characteristic curves for EGC detection and depth prediction were 0.981 and 0.851, respectively. Among the factors affecting AI prediction of tumor depth, only histologic differentiation was significantly…

Background: Although acute kidney injury (AKI) is a frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), the incidence and impact of AKI on mortality among patients on ECMO remain unclear. We conducted this systematic review to summarize the incidence and impact of AKI on mortality risk among adult patients on ECMO. Methods: A literature search was performed using EMBASE, Ovid MEDLINE, and Cochrane Databases from inception until March 2019 to identify studies assessing the incidence of AKI (using a standard AKI definition), severe AKI requiring renal replacement therapy (RRT), and the impact of AKI among adult patients on ECMO. Effect estimates from the individual studies were obtained and combined utilizing random-effects, generic inverse variance method of DerSimonian-Laird. The protocol for this systematic review is registered with PROSPERO (no. CRD42018103527). Results: 41 cohort studies with a total of 10,282 adult patients receiving ECMO were enrolled. Overall, the pooled estimated incidence of AKI and severe AKI requiring RRT were 62.8%…

INTRODUCTION: Clinical guidelines recommend using neuroimaging, Prechtls' General Movements Assessment (GMA), and Hammersmith Infant Neurological Examination (HINE) to diagnose cerebral palsy (CP) in infancy. Previous studies provided excellent sensitivity and specificity for each test in isolation, but no study has examined the pooled predictive power for early diagnosis. METHODS: We performed a retrospective case-control study of 441 high-risk infants born between 2003 and 2014, from three Italian hospitals. Infants with either a normal outcome, mild disability, or CP at two years, were matched for birth year, gender, and gestational age. Three-month HINE, GMA, and neuroimaging were retrieved from medical records. Logistic regression was conducted with log-likelihood and used to determine the model fit and Area Under the Curve (AUC) for accuracy. RESULTS: Sensitivity and specificity for detecting CP were 88% and 62% for three-month HINE, 95% and 97% for absent fidgety GMs, and 79% and 99% for neuroimaging. The combined predictive power of all three assessments gave sensitivity and…

Since the 1800s, there have been calls in the literature for the early diagnosis of cerebral palsy (CP). However, diagnosis still often occurs late, from 12 to 24 months in high income countries and as late as 5 years in low resource settings. This is after the optimal timeframe for applying interventions which could harness neuroplastic potential in the developing brain. Multiple barriers exist which affect clinicians' confidence in diagnosing CP early. These range from the lack of definitive biomarkers to a lack of curative treatments for CP. Further barriers to diagnosis are proposed including; (a) difficulty finding a congruent fit with the definition of CP in an infant, where expected activity limitations might not yet be apparent; and (b) differences in the presentation of motor type and topography classifications between infants and children. These barriers may affect a clinicians' confidence using "pattern recognition" in the differential diagnosis process. One of the central tenets of this paper is that diagnosis and classification are different, involving different…

Peripheral intravenous cannulation is the most common invasive hospital procedure but is associated with a high failure rate. This study aimed to improve the A-DIVA scale (Adult Difficult Intra Venous Access Scale) by external validation, to predict the likelihood of difficult intravenous access in adults. This multicenter study was carried out throughout five hospitals in the Netherlands. Adult participants were included, regardless of their indication for intravenous access, demographics, and medical history. The main outcome variable was defined as failed peripheral intravenous cannulation on the first attempt. A total of 3587 participants was included in this study. The first attempt success rate was 81%. Finally, five variables were included in the prediction model: a history of difficult intravenous cannulation, a difficult intravenous access as expected by the practitioner, the inability to detect a dilated vein by palpating and/or visualizing the extremity, and a diameter of the selected vein less than 3 millimeters. Based on a participant's individual score on the A-DIVA…

Sensory processing issues have been frequently reported in individuals with Autism Spectrum Disorders (ASD), but their relationship with social and overall adaptive functioning has not been extensively characterized to date. Here, we investigate how sensory processing atypicalities relate with deficits in social skills, impaired social cognition, and general adaptive functioning in a group of preschoolers with ASD. Sixty-four children with ASD aged 3 to 6 were included in this study, along with 36 age-matched typically-developing (TD) peers. Parent-reported measures of sensory processing, social difficulties and overall adaptive functioning were collected for all children. We also obtained precise measures of social attention deployment using a custom-design eye-tracking task depicting naturalistic social scenes. Within the group of children with ASD, higher intensities of sensory issues were associated with more prominent social difficulties and lower adaptive functioning. We also found that children with ASD who had more sensory issues showed visual exploration patterns of social…

The aim of our study was to characterize the etiology of prosthetic joint infections (PJIs)—including multidrug-resistant organisms (MDRO)—by category of infection. A multicenter study of 2544 patients with PJIs was performed. We analyzed the causative microorganisms according to the Tsukayama’s scheme (early postoperative, late chronic, and acute hematogenous infections (EPI, LCI, AHI) and “positive intraoperative cultures” (PIC)). Non-hematogenous PJIs were also evaluated according to time since surgery: <1 month, 2–3 months, 4–12 months, >12 months. AHIs were mostly caused by Staphylococcus aureus (39.2%) and streptococci (30.2%). EPIs were characterized by a preponderance of virulent microorganisms (S. aureus, Gram-negative bacilli (GNB), enterococci), MDROs (24%) and polymicrobial infections (27.4%). Conversely, coagulase-negative staphylococci (CoNS) and Cutibacterium species were predominant in LCIs (54.5% and 6.1%, respectively) and PICs (57.1% and 15.1%). The percentage of MDROs isolated in EPIs was more than three times the percentage isolated in LCIs (7.8%) and more than…

Human aging is associated with structural and functional brain deteriorations and a corresponding cognitive decline. Exergaming (i.e., physically active video-gaming) has been supposed to attenuate age-related brain deteriorations and may even improve cognitive functions in healthy older adults. Effects of exergaming, however, vary largely across studies. Moreover, the underlying neurophysiological mechanisms by which exergaming may affect cognitive and brain function are still poorly understood. Therefore, we systematically reviewed the effects of exergame interventions on cognitive outcomes and neurophysiological correlates in healthy older adults (>60 years). After screening 2709 studies (Cochrane Library, PsycINFO, Pubmed, Scopus), we found 15 eligible studies, four of which comprised neurophysiological measures. Most studies reported within group improvements in exergamers and favorable interaction effects compared to passive controls. Fewer studies found superior effects of exergaming over physically active control groups and, if so, solely for executive functions. Regarding…

Poly (ADP-ribose) polymerases (PARPs) play an important role in various cellular processes, such as replication, recombination, chromatin remodeling, and DNA repair. Emphasizing PARP’s role in facilitating DNA repair, the PARP pathway has been a target for cancer researchers in developing compounds which selectively target cancer cells and increase sensitivity of cancer cells to other anticancer agents, but which also leave normal cells unaffected. Since certain tumors (BRCA1/2 mutants) have deficient homologous recombination repair pathways, they depend on PARP-mediated base excision repair for survival. Thus, inhibition of PARP is a promising strategy to selectively kill cancer cells by inactivating complementary DNA repair pathways. Although PARP inhibitor therapy has predominantly targeted BRCA-mutated cancers, this review also highlights the growing conversation around PARP inhibitor treatment for non-BRCA-mutant tumors, those which exhibit BRCAness and homologous recombination deficiency. We provide an update on the field’s progress by considering PARP inhibitor mechanisms,…

Periodontitis is a chronic inflammation that develops due to a destructive tissue response to prolonged inflammation and a disturbed homeostasis (dysbiosis) in the interplay between the microorganisms of the dental biofilm and the host. The infectious nature of the microbes associated with periodontitis is unclear, as is the role of specific bacterial species and virulence factors that interfere with the host defense and tissue repair. This review highlights the impact of classical virulence factors, such as exotoxins, endotoxins, fimbriae and capsule, but also aims to emphasize the often-neglected cascade of metabolic products (e.g., those generated by anaerobic and proteolytic metabolism) that are produced by the bacterial phenotypes that survive and thrive in deep, inflamed periodontal pockets. This metabolic activity of the microbes aggravates the inflammatory response from a low-grade physiologic (homeostatic) inflammation (i.e., gingivitis) into more destructive or tissue remodeling processes in periodontitis. That bacteria associated with periodontitis are linked with a…

Background: The study’s aim was to summarize the incidence and impacts of post-liver transplant (LTx) acute kidney injury (AKI) on outcomes after LTx. Methods: A literature search was performed using the MEDLINE, EMBASE and Cochrane Databases from inception until December 2018 to identify studies assessing the incidence of AKI (using a standard AKI definition) in adult patients undergoing LTx. Effect estimates from the individual studies were derived and consolidated utilizing random-effect, the generic inverse variance approach of DerSimonian and Laird. The protocol for this systematic review is registered with PROSPERO (no. CRD42018100664). Results: Thirty-eight cohort studies, with a total of 13,422 LTx patients, were enrolled. Overall, the pooled estimated incidence rates of post-LTx AKI and severe AKI requiring renal replacement therapy (RRT) were 40.7% (95% CI: 35.4%–46.2%) and 7.7% (95% CI: 5.1%–11.4%), respectively. Meta-regression showed that the year of study did not significantly affect the incidence of post-LTx AKI (p = 0.81). The pooled estimated in-hospital or 30-day…

Autism Spectrum Disorder (ASD) is a complex condition with early childhood onset, characterized by a set of common behavioral features. The etiology of ASD is not yet fully understood; however, it reflects the interaction between genetics and environment. While genetics is now a well-established risk factor, several data support a contribution of the environment as well. This paper summarizes the conclusions of a consensus conference focused on the potential pathogenetic role of environmental factors and on their interactions with genetics. Several environmental factors have been discussed in terms of ASD risk, namely advanced parental age, assisted reproductive technologies, nutritional factors, maternal infections and diseases, environmental chemicals and toxicants, and medications, as well as some other conditions. The analysis focused on their specific impact on three biologically relevant time windows for brain development: the periconception, prenatal, and early postnatal periods. Possible protective factors that might prevent or modify an ASD trajectory have been explored as…

There has been an alarming increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. Uncontrolled T2DM can lead to alterations in the immune system, increasing the risk of susceptibility to infections such as Mycobacterium tuberculosis (M. tb). Altered immune responses could be attributed to factors such as the elevated glucose concentration, leading to the production of Advanced Glycation End products (AGE) and the constant inflammation, associated with T2DM. This production of AGE leads to the generation of reactive oxygen species (ROS), the use of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) via the Polyol pathway, and overall diminished levels of glutathione (GSH) and GSH-producing enzymes in T2DM patients, which alters the cytokine profile and changes the immune responses within these patients. Thus, an understanding of the intricate pathways responsible for the pathogenesis and complications in T2DM, and the development of strategies to enhance the immune system, are both urgently needed to prevent co-infections and co-morbidities in…

The risk of adverse effects of nitrous oxide (N2O) exposure is insufficiently recognized despite its widespread use. These effects are mainly reported through case reports. We conducted an individual patient data meta-analysis to assess the prevalence of clinical, laboratory, and magnetic resonance findings in association with N2O exposure in medical and recreational settings. We calculated the pooled estimates for the studied outcomes and assessed the potential bias related to population stratification using principal component analysis. Eighty-five publications met the inclusion criteria and reported on 100 patients with a median age of 27 years and 57% of recreational users. The most frequent outcomes were subacute combined degeneration (28%), myelopathy (26%), and generalized demyelinating polyneuropathy (23%). A T2 signal hyperintensity in the spinal cord was reported in 68% (57.2–78.8%) of patients. The most frequent clinical manifestations included paresthesia (80%; 72.0–88.0%), unsteady gait (58%; 48.2–67.8%), and weakness (43%; 33.1–52.9%). At least one hematological…

Sarcopenia, defined as the age-related decrease in muscle mass, strength and physical performance, is associated with reduced bone mass and elevated low-grade inflammation. From a healthy aging perspective, interventions which overcome sarcopenia are clinically relevant. Accumulating evidence suggests that exogenous creatine supplementation has the potential to increase aging muscle mass, muscle performance, and decrease the risk of falls and possibly attenuate inflammation and loss of bone mineral. Therefore, the purpose of this review is to: (1) summarize the effects of creatine supplementation, with and without resistance training, in aging adults and discuss possible mechanisms of action, (2) examine the effects of creatine on bone biology and risk of falls, (3) evaluate the potential anti-inflammatory effects of creatine and (4) determine the safety of creatine supplementation in aging adults.

The prevalence of obesity is increasing in the world, and obesity-induced disease, insulin-resistance, cardiovascular disease, and malignancies are becoming a problem. Epidemiological studies have shown that obesity is associated with advanced prostate cancer and that obese men with prostate cancer have a poorer prognosis. Obesity induces systemic inflammation via several mechanisms. High-fat diet-induced prostate cancer progresses via adipose-secretory cytokines or chemokines. Inflammatory cells play important roles in tumor progression. A high-fat diet or obesity changes the local profile of immune cells, such as myeloid-derived suppressor cells and macrophages, in prostate cancer. Tumor-associated neutrophils, B cells, and complements may promote prostate cancer in the background of obesity. Interventions to control systemic and/or local inflammation and changes in lifestyle may also be viable therapies for prostate cancer.

Background: Depression is commonly treated with anti-depressant medication and/or psychological interventions. Patients with depression are common users of complementary therapies, such as acupuncture, either as a replacement for, or adjunct to, their conventional treatments. This systematic review and meta-analysis examined the effectiveness of acupuncture in major depressive disorder. Methods: A search of English (Medline, PsychINFO, Google Scholar, and CINAL), Chinese (China National Knowledge Infrastructure Database (CNKI) and Wanfang Database), and Korean databases was undertaken from 1980 to November 2018 for clinical trials using manual, electro, or laser acupuncture. Results: Twenty-nine studies including 2268 participants were eligible and included in the meta-analysis. Twenty-two trials were undertaken in China and seven outside of China. Acupuncture showed clinically significant reductions in the severity of depression compared to usual care (Hedges (g) = 0.41, 95% confidence interval (CI) 0.18 to 0.63), sham acupuncture (g = 0.55, 95% CI 0.31 to 0.79), and as an adjunct…

Epithelial-to-mesenchymal transition (EMT) programs contribute to the acquisition of invasive properties that are essential for metastasis. It is well established that EMT programs alter cell state and promote invasive behavior. This review discusses how rather than following one specific program, EMT states are diverse in their regulation and invasive properties. Analysis across a spectrum of models using a combination of approaches has revealed how unique features of distinct EMT programs dictate whether tumor cells invade as single cells or collectively as cohesive groups of cells. It has also been shown that the mode of collective invasion is determined by the nature of the EMT, with cells in a trailblazer-type EMT state being capable of initiating collective invasion, whereas cells that have undergone an opportunist-type EMT are dependent on extrinsic factors to invade. In addition to altering cell intrinsic properties, EMT programs can influence invasion through non-cell autonomous mechanisms. Analysis of tumor subpopulations has demonstrated how EMT-induced cells can drive…

Adipose tissue stem cells (ASCs), known as multipotent stem cells, are most commonly used in the clinical applications in recent years. Adipose tissues (AT) have the advantage in the harvesting, isolation, and expansion of ASCs, especially an abundant amount of stem cells compared to bone marrow. ASCs can be found in stromal vascular fractions (SVF) which are easily obtained from the dissociation of adipose tissue. Both SVFs and culture-expanded ASCs exhibit the stem cell characteristics such as differentiation into multiple cell types, regeneration, and immune regulators. Therefore, SVFs and ASCs have been researched to evaluate the safety and benefits for human use. In fact, the number of clinical trials on ASCs is going to increase by years; however, most trials are in phase I and II, and lack phase III and IV. This systemic review highlights and updates the process of the harvesting, characteristics, isolation, culture, storage, and application of ASCs, as well as provides further directions on the therapeutic use of ASCs.

Drugs of abuse are associated with stroke, especially in young individuals. The major classes of drugs linked to stroke are cocaine, amphetamines, heroin, morphine, cannabis, and new synthetic cannabinoids, along with androgenic anabolic steroids (AASs). Both ischemic and hemorrhagic stroke have been reported due to drug abuse. Several common mechanisms have been identified, such as arrhythmias and cardioembolism, hypoxia, vascular toxicity, vascular spasm and effects on the thrombotic mechanism, as causes for ischemic stroke. For hemorrhagic stroke, acute hypertension, aneurysm formation/rupture and angiitis-like changes have been implicated. In AAS abuse, the effect of blood pressure is rather substance specific, whereas increased erythropoiesis usually leads to thromboembolism. Transient vasospasm, caused by synthetic cannabinoids, could lead to ischemic stroke. Opiates often cause infective endocarditis, resulting in ischemic stroke and hypereosinophilia accompanied by pyogenic arthritis, provoking hemorrhagic stroke. Genetic variants are linked to increased risk for stroke in…

BACKGROUND: 'Gaming Disorder' (GD) has received increased medical attention and official recognition from both the American Psychiatric Association (APA) and the World Health Organization (WHO). Although these two medical organizations have independently developed promising clinical diagnostic frameworks to assess disordered gaming, little is known about how these frameworks compare at different psychometric levels in terms of producing consistent outcomes in the assessment of GD. METHODS: = 29.74 years; SD = 12.37 years) completed an online survey including measures on different psychopathological symptoms (depression, loneliness and attention problems), gaming motives and disordered gaming according to the WHO and APA frameworks. RESULTS: The findings suggest the existence of minor discrepancies in the estimation of prevalence rates of GD according among the two frameworks. Nevertheless, both diagnostic frameworks are fairly consistent in the psychometric prediction of GD in relation to gaming motives and psychopathological symptoms. The findings underscore the role of key gaming…

Numerous studies have previously evaluated the marginal and internal fit of fixed prostheses; however, few reports have performed an objective comparison of the various methods used for their assessment. The purpose of this study was to compare five marginal and internal fit assessment methods for fixed prostheses. A specially designed sample was used to measure the marginal and internal fit of the prosthesis according to the cross-sectional method (CSM), silicone replica technique (SRT), triple scan method (TSM), micro-computed tomography (MCT), and optical coherence tomography (OCT). The five methods showed significant differences in the four regions that were assessed (p < 0.001). The marginal, axial, angle, and occlusal regions showed low mean values: CSM (23.2 µm), TSM (56.3 µm), MCT (84.3 µm), and MCT (102.6 µm), respectively. The marginal fit for each method was in the range of 23.2–83.4 µm and internal fit (axial, angle, and occlusal) ranged from 44.8–95.9 µm, 84.3–128.6 µm, and 102.6–140.5 µm, respectively. The marginal and internal fit showed significant differences…

Cadmium (Cd), a nonbiodegradable heavy metal and one of the most neurotoxic environmental and industrial pollutants, promotes disturbances in major organs and tissues following both acute and chronic exposure. In this study, we assessed the neuroprotective potential of caffeine (30 mg/kg) against Cd (5 mg/kg)-induced oxidative stress-mediated neuroinflammation, neuronal apoptosis, and cognitive deficits in male C57BL/6N mice in vivo and in HT-22 and BV-2 cell lines in vitro. Interestingly, our findings indicate that caffeine markedly reduced reactive oxygen species (ROS) and lipid peroxidation (LPO) levels and enhanced the expression of nuclear factor-2 erythroid-2 (Nrf-2) and hemeoxygenase-1 (HO-1), which act as endogenous antioxidant regulators. Also, 8-dihydro-8-oxoguanine (8-OXO-G) expression was considerably reduced in the caffeine-treated group as compared to the Cd-treated group. Similarly, caffeine ameliorated Cd-mediated glial activation by reducing the expression of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), and other…

Chronic pain is a prevalent and persistent problem in middle childhood and adolescence. The biopsychosocial model of pain, which accounts for the complex interplay of the biological, psychological, social, and environmental factors that contribute to and maintain pain symptoms and related disability has guided our understanding and treatment of pediatric pain. Consequently, many interventions for chronic pain are within the realm of rehabilitation, based on the premise that behavior has a broad and central role in pain management. These treatments are typically delivered by one or more providers in medicine, nursing, psychology, physical therapy, and/or occupational therapy. Current data suggest that multidisciplinary treatment is important, with intensive interdisciplinary pain rehabilitation (IIPT) being effective at reducing disability for patients with high levels of functional disability. The following review describes the current state of the art of rehabilitation approaches to treat persistent pain in children and adolescents. Several emerging areas of interventions are also…

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with a complex symptomatology, and core symptoms as well as functional impairment often persist into adulthood. Recent investigations estimate the worldwide prevalence of ADHD in children and adolescents to be ~7%, which is a substantial increase compared to a decade ago. Conventional treatment most often includes pharmacotherapy with central nervous stimulants, but the number of non-responders and adverse effects call for treatment alternatives. Exercise has been suggested as a safe and low-cost adjunctive therapy for ADHD and is reported to be accompanied by positive effects on several aspects of cognitive functions in the general child population. Here we review existing evidence that exercise affects cognitive functions in children with and without ADHD and present likely neurophysiological mechanisms of action. We find well-described associations between physical activity and ADHD, as well as causal evidence in the form of small to moderate beneficial effects following acute aerobic exercise on…

Anorexia nervosa is the most severe eating disorder; it has a protracted course of illness and the highest mortality rate among all psychiatric illnesses. It is characterised by a restriction of energy intake followed by substantial weight loss, which can culminate in cachexia and related medical consequences. Anorexia nervosa is associated with high personal and economic costs for sufferers, their relatives and society. Evidence-based practice guidelines aim to support all groups involved in the care of patients with anorexia nervosa by providing them with scientifically sound recommendations regarding diagnosis and treatment. The German S3-guideline for eating disorders has been recently revised. In this paper, the new guideline is presented and changes, in comparison with the original guideline published in 2011, are discussed. Further, the German guideline is compared to current international evidence-based guidelines for eating disorders. Many of the treatment recommendations made in the revised German guideline are consistent with existing international treatment guidelines.…

In chronic kidney disease (CKD), the gut-microbiota metabolites indoxyl sulfate (IS) and p-cresyl sulfate (PCS) progressively accumulate due to their high albumin-binding capacity, leading to clinical complications. In a prospective crossover controlled trial, 60 patients with CKD grades 3B–4 (GFR = 21.6 ± 13.2 mL/min) were randomly assigned to two dietary regimens: (i) 3 months of free diet (FD) (FD is the diet usually used by the patient before being enrolled in the Medika study), 6 months of very low protein diet (VLPD), 3 months of FD and 6 months of Mediterranean diet (MD); (ii) 3 months of FD, 6 months of MD, 3 months of FD, and 6 months of VLPD. VLPD reduced inflammatory Proteobacteria and increased Actinobacteria phyla. MD and VLPD increased some butyrate-forming species of Lachnospiraceae, Ruminococcaceae, Prevotellaceae, Bifidobacteriaceae, and decrease the pathobionts Enterobacteriaceae. The increased level of potential anti-inflammatory Blautia and Faecalibacterium, as well as butyrate-forming Coprococcus and Roseburia species in VLPD was positively associated with…

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal mucosa and unknown etiology. In this review, we identified three main eras in the IBD history. Between the 19th and the 20th century, the primary task had been the definition of the diagnostic criteria in order to differentiate the new entity from intestinal tuberculosis. In the 20th century, an intense and prolific therapeutic research prevailed, culminating in the introduction of biological drugs in the clinical setting. Since the beginning of the 21st century, traditional definition criteria have been challenged by holistic criteria in an effort to seek a still unattained cure. Centuries of worldwide efforts on IBD etiology and therapy search have culminated in this novel strategy.

The repair of bone defects caused by trauma, infection or tumor resection is a major clinical orthopedic challenge. The application of bone grafts in orthopedic procedures is associated with a problem of inadequate vascularization in the initial phase after implantation. Meanwhile, the survival of cells within the implanted graft and its integration with the host tissue is strongly dependent on nutrient and gaseous exchange, as well as waste product removal, which are effectuated by blood microcirculation. In the bone tissue, the vasculature also delivers the calcium and phosphate indispensable for the mineralization process. The critical role of vascularization for bone healing and function, led the researchers to the idea of generating a capillary-like network within the bone graft in vitro, which could allow increasing the cell survival and graft integration with a host tissue. New strategies for engineering pre-vascularized bone grafts, that apply the co-culture of endothelial and bone-forming cells, have recently gained interest. However, engineering of metabolically active…

Curcumin and o-Vanillin cleared senescent intervertebral disc (IVD) cells and reduced the senescence-associated secretory phenotype (SASP) associated with inflammation and back pain. Cells from degenerate and non-mildly-degenerate human IVD were obtained from organ donors and from patients undergoing surgery for low back pain. Gene expression of senescence and SASP markers was evaluated by RT-qPCR in isolated cells, and protein expression of senescence, proliferation, and apoptotic markers was evaluated by immunocytochemistry (ICC). The expression levels of SASP factors were evaluated by enzyme-linked immunosorbent assay (ELISA). Matrix synthesis was verified with safranin-O staining and the Dimethyl-Methylene Blue Assay for proteoglycan content. Western blotting and ICC were used to determine the molecular pathways targeted by the drugs. We found a 40% higher level of senescent cells in degenerate compared to non-mildly-degenerate discs from unrelated individuals and a 10% higher level in degenerate compared to non-mildly-degenerate discs from the same individual. Higher levels of…

Helicobacter pylori is a major human pathogen. Diagnosis of H. pylori infection and determination of its antibiotic susceptibility still mainly rely on culture and phenotypic drug susceptibility testing (DST) that is time-consuming and laborious. Whole genome sequencing (WGS) has recently emerged in medical microbiology as a diagnostic tool for reliable drug resistance prediction in bacterial pathogens. The aim of this study was to compare phenotypic DST results with the predictions based on the presence of genetic determinants identified in the H. pylori genome using WGS. Phenotypic resistance to clarithromycin, metronidazole, tetracycline, levofloxacin, and rifampicin was determined in 140 clinical H. pylori isolates by E-Test®, and the occurrence of certain single nucleotide polymorphisms (SNPs) in target genes was determined by WGS. Overall, there was a high congruence of >99% between phenotypic DST results for clarithromycin, levofloxacin, and rifampicin and SNPs identified in the 23S rRNA, gyrA, and rpoB gene. However, it was not possible to infer a resistance phenotype for…

Although moderate concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are crucial for various physiological processes within the human body, their overproduction leads to oxidative stress, defined as the imbalance between the production and accumulation of ROS and the ability of the body to neutralize and eliminate them. In the brain, oxidative stress exhibits significant effects, due to its increased metabolical activity and limited cellular regeneration. Thus, oxidative stress is a major factor in the progressive loss of neurons structures and functions, leading to the development of severe neurodegenerative disorders. In this context, recent years have witnessed tremendous advancements in the field of antioxidant therapies, with a special emphasis for neuroprotection. The aim of this paper is to provide an overview of the oxidative stress and antioxidant defense mechanisms and to present the most recent studies on antioxidant therapies for neuroprotection.

Focusing on previously published mechanisms of non-alcoholic fatty liver disease (NAFLD), their uncertainty does not always permit a clear elucidation of the grassroot alterations that are at the basis of the wide-spread illness, and thus curing it is still a challenge. There is somehow exceptional progress, but many controversies persist in NAFLD research and clinical investigation. It is likely that hidden mechanisms will be brought to light in the near future. Hereby, the authors present, with some criticism, classical mechanisms that stand at the basis of NAFLD, and consider contextually different emerging processes. Without ascertaining these complex interactions, investigators have a long way left ahead before finding an effective therapy for NAFLD beyond diet and exercise.

Liquid biopsy is a technique that utilizes circulating biomarkers in the body fluids of cancer patients to provide information regarding the genetic landscape of the cancer. It is emerging as an alternative and complementary diagnostic and prognostic tool to surgical biopsy in oncology. Liquid biopsy focuses on the detection and isolation of circulating tumor cells, circulating tumor DNA and exosomes, as a source of genomic and proteomic information in cancer patients. Liquid biopsy is expected to provide the necessary acceleratory force for the implementation of precision oncology in clinical settings by contributing an enhanced understanding of tumor heterogeneity and permitting the dynamic monitoring of treatment responses and genomic variations. However, widespread implementation of liquid biopsy based biomarker-driven therapy in the clinical practice is still in its infancy. Technological advancements have resolved many of the hurdles faced in the liquid biopsy methodologies but sufficient clinical and technical validation for specificity and sensitivity has not yet been…

Adipose-derived stem cells (ASCs) have been routinely used from several years in regenerative surgery without any definitive statement about their potential pro-oncogenic or anti-oncogenic role. ASCs has proven to favor tumor progression in several experimental cancer models, playing a central role in regulating tumor invasiveness and metastatic potential through several mechanisms, such as the paracrine release of exosomes containing pro-oncogenic molecules and the induction of epithelial-mesenchymal transition. However, the high secretory activity and the preferential tumor-targeting make also ASCs a potentially suitable vehicle for delivery of new anti-cancer molecules in tumor microenvironment. Nanotechnologies, viral vectors, drug-loaded exosomes, and micro-RNAs (MiR) represent additional new tools that can be applied for cell-mediated drug delivery in a tumor microenvironment. Recent studies revealed that the MiR play important roles in paracrine actions on adipose-resident macrophages, and their dysregulation has been implicated in the pathogenesis of obesity, diabetes, and…

The bacterial species, Helicobacter pylori, is associated with several gastrointestinal diseases, and poses serious health threats owing to its resistance to antibiotics. Lactobacillus spp., on the other hand, possess probiotic activities that have beneficial effects in humans. However, the mechanisms by which Lactobacillus spp. harbor favorable functions and act against H. pylori infection remain to be explored. The aim of this study was to investigate the ability of bacterial strains, Lactobacillus rhamnosus and Lactobacillus acidophilus, termed GMNL-74 and GMNL-185, respectively, to inhibit H. pylori growth and inflammation. Our results showed that GMNL-74 and GMNL-185 possess potent antimicrobial activity against multidrug resistant (MDR)-H. pylori. In addition, an in vitro cell-based model revealed that the inhibition of H. pylori adhesion and invasion of gastric epithelial cells and interleukin-8 production were significantly decreased by treatment with both the Lactobacillus strains. In vivo studies demonstrated that colonization of H. pylori and induced inflammation in the…

Hyperspectral/Multispectral imaging (HSI/MSI) technologies are able to sample from tens to hundreds of spectral channels within the electromagnetic spectrum, exceeding the capabilities of human vision. These spectral techniques are based on the principle that every material has a different response (reflection and absorption) to different wavelengths. Thereby, this technology facilitates the discrimination between different materials. HSI has demonstrated good discrimination capabilities for materials in fields, for instance, remote sensing, pollution monitoring, field surveillance, food quality, agriculture, astronomy, geological mapping, and currently, also in medicine. HSI technology allows tissue observation beyond the limitations of the human eye. Moreover, many researchers are using HSI as a new diagnosis tool to analyze optical properties of tissue. Recently, HSI has shown good performance in identifying human diseases in a non-invasive manner. In this paper, we show the potential use of these technologies in the medical domain, with emphasis in the current advances in…

Immune checkpoint inhibitor (ICI) therapy has revolutionized the management of various cancers with previously poor prognosis. Despite its great efficacy, the therapy is associated with a wide spectrum of immune-related adverse events (irAE) including neurological symptoms which can affect all parts of the central and peripheral nervous system. Even though these events are rare, they are of high relevance as the rate of residual symptoms or even fatal outcomes is remarkable. To provide a detailed overview of neurological adverse events associated with immune checkpoint-inhibitor therapy we conducted a literature search. While focusing on ipilimumab, nivolumab, and pembrolizumab therapy, all available case reports as well as larger case series and clinical trials have been considered. Eighty-two case reports about checkpoint-inhibitor therapy induced symptoms of the peripheral nervous system have been published, while only 43 case reports addressed central nervous system abnormalities. The frequency of immune checkpoint-inhibitor therapy inducing neurological adverse events is about…

Background and Aims: Inflammatory bowel disease (IBD) may be associated with anxiety and depression. The aim of this study was to evaluate the incidence of anxiety and depression in patients with IBD compared to the general population. Methods: A nationwide population-based cohort study was conducted using claims data from the National Healthcare Insurance service in Korea. We compared the incidence of anxiety and depression between 15,569 IBD patients and 46,707 non-IBD controls, age and sex matched at a ratio of 1:3. Results: During a mean follow-up of six years, IBD patients experienced significantly more anxiety (12.2% vs. 8.7%; p < 0.001) and depression (8.0% vs. 4.7%; p < 0.001) compared to controls. The curves showing cumulative incidences of anxiety and depression showed a steep rise within one year following a diagnosis of IBD, leading to lines with a constant slope. The hazard ratio (HR) for new onset anxiety following a diagnosis of Crohn’s disease (CD) and ulcerative colitis (UC) was 1.63 and 1.60, respectively, compared to controls (p < 0.001). Compared to controls, the…

Background: Chronic pain may be treated by medical cannabis. Yet, there is scarce evidence to support the role of medical cannabis in the treatment of fibromyalgia. The aim of the study was to investigate the characteristics, safety, and effectiveness of medical cannabis therapy for fibromyalgia. Methods: A prospective observational study with six months follow-up period based on fibromyalgia patients who were willing to answer questionnaire in a specialized medical cannabis clinic between 2015 and 2017. Results: Among the 367 fibromyalgia patients, the mean age was 52.9 ± 15.1, of whom 301 (82.0%) were women. Twenty eight patients (7.6%) stopped the treatment prior to the six months follow-up. The six months response rate was 70.8%. Pain intensity (scale 0–10) reduced from a median of 9.0 at baseline to 5.0 (p < 0.001), and 194 patients (81.1%) achieved treatment response. In a multivariate analysis, age above 60 years (odds ratio [OR] 0.34, 95% C.I 0.16–0.72), concerns about cannabis treatment (OR 0.36, 95% C.I 0.16–0.80), spasticity (OR 2.26, 95% C.I 1.08–4.72), and previous use…

BACKGROUND: High blood pressure has been associated with an increased risk of developing cognitive impairment. However, this relationship is unclear. This study aims to systematically review the effects of blood pressure on executive functioning, language, memory, attention and processing speed. METHODS: The review process was conducted according to the PRISMA-Statement, using the PubMed, PsycINFO, PsycARTICLES and MEDLINE databases. Restrictions were made by selecting studies, which included one or more cognitive measures and reported blood pressure recordings. Studies that included participants with medical conditions or people diagnosed with dementia, psychiatric disorders, stroke and head trauma were excluded. The review allows selecting fifty studies that included 107,405 participants. The results were reported considering different cognitive domains separately: global cognitive functioning, attention, processing speed, executive functions, memory and visuospatial abilities. RESULTS: Higher blood pressure appears to influence cognitive performance in different domains in the…

The widespread epidemic of obesity and type 2 diabetes (T2D), suggests that both disorders are closely linked. Several pre-clinical and clinical studies have showed that adipose-derived mesenchymal stem cells (ASC) transplantation is efficient and safe. Moreover, scientists have already highlighted the therapeutic capacity of their secretomes. In this study, we used quantitative PCR, a flow cytometry-based system, the ELISA method, spectrophotometry, and confocal and scanning electron microscopy, to compare the differences in proliferation activity, viability, morphology, mitochondrial dynamics, mRNA and miRNA expression, as well as the secretory activity of ASCs derived from two donor groups—non-diabetic and T2D patients. We demonstrated that ASCs from T2D patients showed a reduced viability and a proliferative potential. Moreover, they exhibited mitochondrial dysfunction and senescence phenotype, due to excessive oxidative stress. Significant differences were observed in the expressions of miRNA involved in cell proliferations (miR-16-5p, miR-146a-5p, and miR-145-5p), as well as…

Structural and functional collapse of the balance between excitatory (E) and inhibitory (I) synapses, i.e., synaptic E/I balance, underlies the pathogeneses of various central nervous system (CNS) disorders. In epilepsy, the synaptic E/I balance tips toward excitation; thus, most of the existing epileptic remedies have focused on how to directly suppress the activity of neurons. However, because as many as 30% of patients with epilepsy are drug resistant, the discovery of new therapeutic targets is strongly desired. Recently, the roles of glial cells in epilepsy have gained attention because glial cells manipulate synaptic structures and functions in addition to supporting neuronal survival and growth. Among glial cells, microglia, which are brain-resident immune cells, have been shown to mediate inflammation, neuronal death and aberrant neurogenesis after epileptic seizures. However, few studies have investigated the involvement of synaptic pruning-one of the most important roles of microglia-in the epileptic brain. In this review, we propose and discuss the hypothesis that…

Influenza viruses, since time immemorial, have been the major respiratory pathogen known to infect a wide variety of animals, birds and reptiles with established lineages. They belong to the family Orthomyxoviridae and cause acute respiratory illness often during local outbreaks or seasonal epidemics and occasionally during pandemics. Recent studies have identified a new genus within the Orthomyxoviridae family. This newly identified pathogen, D/swine/Oklahoma/1334/2011 (D/OK), first identified in pigs with influenza-like illness was classified as the influenza D virus (IDV) which is distantly related to the previously characterized human influenza C virus. Several other back-to-back studies soon suggested cattle as the natural reservoir and possible involvement of IDV in the bovine respiratory disease complex was established. Not much is known about its likelihood to cause disease in humans, but it definitely poses a potential threat as an emerging pathogen in cattle-workers. Here, we review the evolution, epidemiology, virology and pathobiology of influenza D virus and the…

Polycystic Ovary Syndrome (PCOS) is a complex condition with mechanisms likely to involve the interaction between genetics and lifestyle. Familial clustering of PCOS symptoms is well documented, providing evidence for a genetic contribution to the condition. This overview aims firstly to systematically summarise the current literature surrounding genetics and PCOS, and secondly, to assess the methodological quality of current systematic reviews and identify limitations. Four databases were searched to identify candidate gene systematic reviews, and quality was assessed with the AMSTAR tool. Genome-wide association studies (GWAS) were identified by a semi structured literature search. Of the candidate gene systematic reviews, 17 were of high to moderate quality and four were of low quality. A total of 19 gene loci have been associated with risk of PCOS in GWAS, and 11 of these have been replicated across two different ancestries. Gene loci were located in the neuroendocrine, metabolic, and reproductive pathways. Overall, the gene loci with the most robust findings were THADA, FSHR,…

Chronic Low Back Pain (CLBP) is a major and highly prevalent health problem. Given the high number of papers available, clinicians might be overwhelmed by the evidence on CLBP management. Taking into account the scale and costs of CLBP, it is imperative that healthcare professionals have access to up-to-date, evidence-based information to assist them in treatment decision-making. Therefore, this paper provides a state-of-the-art overview of the best evidence non-invasive rehabilitation for CLBP. Taking together up-to-date evidence from systematic reviews, meta-analysis and available treatment guidelines, most physically inactive therapies should not be considered for CLBP management, except for pain neuroscience education and spinal manipulative therapy if combined with exercise therapy, with or without psychological therapy. Regarding active therapy, back schools, sensory discrimination training, proprioceptive exercises, and sling exercises should not be considered due to low-quality and/or conflicting evidence. Exercise interventions on the other hand are recommended, but while…

Diabetic foot ulcers (DFUs) and diabetic foot infections (DFIs) are associated with reduced patient quality of life, lower-extremity amputation, hospitalization, and high morbidity and mortality. Diverse bacterial communities have been identified in DFUs/DFIs, playing a significant role in infection prognosis. However, due to the high heterogeneity of bacterial communities colonized in DFUs/DFIs, culture-based methods may not isolate all of the bacterial population or unexpected microorganisms. Recently, high sensitivity and specificity of DNA (metagenomics) and RNA (metatranscriptomics) technologies have addressed limitations of culture-based methods and have taken a step beyond bacterial identification. As a consequence, new advances obtained from DNA- and RNA-based techniques for bacterial identification can improve therapeutic approaches. This review evaluated the current state of play in aetiology of DFUs/DFIs on culture and molecular approaches, and discussed the impact of metagenomic and metatranscriptomic methods in bacterial identification approaches.

Objective: the objective of this review is to analyze the advances in the field of rehabilitation through virtual reality, while taking into account non-immersive systems, as evidence have them shown to be highly accepted by older people, due to the lowest "cibersikness" symptomatology. DATA SOURCES: a systematic review of the literature was conducted in June 2019. The data were collected from Cochrane, Embase, Scopus, and PubMed databases, analyzing manuscripts and articles of the last 10 years. STUDY SELECTION: we only included randomized controlled trials written in English aimed to study the use of the virtual reality in rehabilitation. We selected 10 studies, which were characterized by clinical heterogeneity. DATA EXTRACTION: quality evaluation was performed based on the Physioterapy Evidence Database (PEDro) scale, suggested for evidence based review of stroke rehabilitation. Of 10 studies considered, eight were randomized controlled trials and the PEDro score ranged from four to a maximum of nine. DATA SYNTHESIS: VR (Virtual Reality) creates artificial environments with the…

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and affects millions worldwide. Due to the lack of effective systemic therapies for HCC, researchers have been investigating the use of locoregional tumor control with Yttrium-90 (Y90) radioembolization since the 1960s. Following the development of glass and resin Y90 microspheres in the early 1990s, Y90 radioembolization has been shown to be a safe and efficacious treatment for patients with HCC across Barcelona Clinic Liver Cancer (BCLC) stages. By demonstrating durable local control, good long term outcomes, and equivalent if not superior tumor responses and tolerability when compared to alternative therapies including transarterial chemoembolization (TACE) and sorafenib, Y90 radioembolization is being increasingly used in HCC treatment. More recently, investigations into variations in Y90 radioembolization technique including radiation segmentectomy and radiation lobectomy have further expanded its clinical utility. Here, we discuss the history and evolution of Y90 use in HCC. We outline key clinical…

We aimed to investigate the association of gut microbiota with disease activity, inflammatory parameters, and auto-antibodies profile in rheumatoid arthritis (RA). A total of 138 RA patients and 21 healthy controls (HC) were enrolled. Fecal samples were collected for bacterial DNA extraction and 16S ribosome (r)RNA sequencing, followed by analyses of gut microbiota composition. Serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-17A were determined by using ELISA. Our results indicated that RA patients had lower diversity index, which reflects both evenness and richness of gut microbiota, compared to HC. The alpha-diversity was lower in anti-citrullinated peptide antibodies (ACPA)-positive patients than in HC. The phylum Verrucomicrobiae and genus Akkermansia were more abundant in patients compared to HC. There was increased relative abundance of Enterobacteriaceae as well as Klebsiella, and less abundance of Bifidobacterium in patients with high levels of TNF-α or IL-17A compared to those who had low levels of these cytokines. In addition, ACPA-positive…

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology characterized by immune-mediated damage of synovial joints and antibodies to citrullinated antigens. Periodontal disease, a bacterial-induced inflammatory disease of the periodontium, is commonly observed in RA and has implicated periodontal pathogens as potential triggers of the disease. In particular, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans have gained interest as microbial candidates involved in RA pathogenesis by inducing the production of citrullinated antigens. Here, we will discuss the clinical and mechanistic evidence surrounding the role of these periodontal bacteria in RA pathogenesis, which highlights a key area for the treatment and preventive interventions in RA.

Problems arising from hypersexual behavior are often seen in clinical settings. We aimed to extend the knowledge about the clinical characteristics of individuals with hypersexual disorder (HD). A group of people who fulfilled the proposed diagnostic criteria for HD (men with HD, n = 50) was compared to a group of healthy controls (n = 40). We investigated differences in sociodemographic, neurodevelopmental, and family factors based on self-report questionnaires and clinical interviews. Men with HD reported elevated rates of sexual activity, paraphilias, consumption of child abusive images, and sexual coercive behavior compared to healthy controls. Moreover, rates of affective disorders, attachment difficulties, impulsivity, and dysfunctional emotion regulation strategies were higher in men with HD. Men with HD seem to have experienced various forms of adverse childhood experiences, but there were no further differences in sociodemographic, neurodevelopmental factors, and family factors. Regression analyses indicated that attachment-related avoidance and early onset of masturbation…

In addition to their cholesterol-lowering effects, statins are associated with pleiotropic effects including improvements in heart failure (HF), reduced blood pressure, prevention of the rupture of atherosclerotic plaques and improved angiogenesis. In addition to these cardiovascular benefits, statins have been implicated in the treatment of neurological injuries, cancer, sepsis, and cirrhosis. These cholesterol-independent beneficial effects of statins are predominantly mediated through signaling pathways leading to increased production and bioavailability of nitric oxide (NO). In this review, the mechanistic pathways and therapeutic effects of statin-mediated elevations of NO are described and discussed.

Obstructive sleep apnea (OSA) is the most common sleep disorder. Sleep bruxism (SB) is a masticatory muscle activity during sleep that commonly co-occurs with OSA. The presented study aimed to assess this relationship and to identify factors affecting this co-occurrence. Adult patients (n = 110) were evaluated for OSA and SB in a sleep laboratory using polysomnography. The episodes of bruxism and respiratory events were scored according to the standards of the American Academy of Sleep Medicine. The prevalence of OSA and SB was found to be 86.37% and 50%, respectively. The bruxism episode index (BEI) was increased in the group with mild and moderate OSA (apnea–hypopnea index (AHI) <30) compared to that in the group with severe OSA (AHI ≥ 30) (5.50 ± 4.58 vs. 1.62 ± 1.28, p < 0.05). A positive correlation between AHI and BEI was observed in the group with AHI < 30. Regression analysis indicated that higher AHI, male gender, and diabetes were independent predictors for the increased BEI in group with AHI < 30. The relationship between OSA and SB depends on the degree of severity of…

Alpha 2-Heremans-Schmid glycoprotein, also known as fetuin-A (Fet-A), is a multifunctional plasma glycoprotein that has been identified in both animal and human beings. The protein is a hepatokine predominantly synthesized in the liver, which is considered as an important component of diverse normal and pathological processes, including bone metabolism regulation, vascular calcification, insulin resistance, and protease activity control. Epidemiological studies have already consistently demonstrated significant elevated circulating Fet-A in the course of obesity and related complications, such as type 2 diabetes mellitus, metabolic syndrome, and nonalcoholic fatty liver disorder (NAFLD). Moreover, Fet-A has been strongly correlated with many parameters related to metabolic homeostasis dysregulation, such as insulin sensitivity, glucose tolerance, circulating lipid levels (non-esterified free fatty acids and triglycerides), and circulating levels of both pro- and anti-inflammatory factors (C-reactive protein, tumor necrosis factor-α (TNF-α), and interleukin (IL)-6).…

The study aims to explore the oxidative status related to inflammation in peripheral blood of stable relapsing-remitting multiple sclerosis (MS) patients with low disability. In this study, 31 people were included and divided into two groups: an MS group in which 16 relapsing-remitting MS patients with a low disability level (age 38.9 ± 7.08, EDSS median 2.5) were included and a control group that contains 15 healthy volunteers of similar age to the MS group. Thiobarbituric acid reactive substances (TBARS), protein carbonyl level (PCO), total antioxidant capacity (TAC) as oxidative stress markers, neutrophil/lymphocyte ratio (NLR), and erythrocyte sedimentation rate (ESR) were analyzed in the peripheral blood sample of the healthy and the MS patients to establish the oxidative stress/inflammatory level using conventional plasma markers. In this study, we showed that the pro-inflammatory status of the relapse-remitting stage of diseases can be easily and accurately appreciated by NLR. An increased NLR is associated with a decreased antioxidant capacity, even in the early stage of…

This study aimed to investigate the association between a dual-task intervention program and cognitive and physical functions. In a randomized controlled trial, we enrolled 49 individuals with MCI. The MCI diagnosis was based on medical evaluations through a clinical interview conducted by a dementia specialist. Cognitive assessments were performed by neuropsychologists according to standardized methods, including the MMSE and modified Alzheimer's disease Assessment Scale-Cognitive Subscale (ADAS-Cog), both at baseline and at 3 months follow-up. The program comprised physical activity and behavior modification, aerobic exercise, and a cognitive and exercise combined intervention program. Analysis of the subjects for group-time interactions revealed that the exercise group exhibited a significantly improved ADAS-Cog, working memory, and executive function. Total physical activity levels were associated with improvements in working memory function and the modified ADAS-Cog score, and the associations were stronger for daily moderate intensity activity than for daily step count. The…