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Topic Review
ATR Pathway as a Therapeutic Target for Cancer
The DNA damage response (DDR) system is a complicated network of signaling pathways that detects and repairs DNA damage or induces apoptosis. Critical regulators of the DDR network include the DNA damage kinases ataxia telangiectasia mutated Rad3-related kinase (ATR) and ataxia-telangiectasia mutated (ATM). The ATR pathway coordinates processes such as replication stress response, stabilization of replication forks, cell cycle arrest, and DNA repair. ATR inhibition disrupts these functions, causing a reduction of DNA repair, accumulation of DNA damage, replication fork collapse, inappropriate mitotic entry, and mitotic catastrophe. Data have shown that the inhibition of ATR can lead to synthetic lethality in ATM-deficient malignancies. In addition, ATR inhibition plays a significant role in the activation of the immune system by increasing the tumor mutational burden and neoantigen load as well as by triggering the accumulation of cytosolic DNA and subsequently inducing the cGAS-STING pathway and the type I IFN response. 
  • 163
  • 08 Mar 2024
Topic Review
Atrial Fibrillation and Heart Failure
Atrial Fibrillation (AF) and Heart Failure (HF) are closely linked to each other, as each can be either the cause of or the result of the other. Successfully treating one of the two entities means laying the basis for treating the other one as well. AF is the most common cardiac arrhythmia, It is predisposed by several risk factors such as HF, ischemic heart disease, high blood pressure, valvular heart disease, sleep apnea, and diabetes, and at the same time increases the risk of developing heart failure of any kind (heart failure with preserved ejection fraction, HFpEF; heart failure with mid-range ejection fraction, HFmrEF; heart failure with reduced ejection fraction, HFrEF). AF and heart failure co-exist in up to 30% of patients and are closely linked to each other, as each can be either the cause of or the result of the other (“Atrial Fibrillation Begets Heart Failure and Vice Versa”). When both conditions occur in the same patient, the prognosis is worse than with either condition alone. Pulmonary Vein Isolation (PVI) is a well established treatment option in patients with symptomatic atrial fibrillation. Studies investigating PVI in patients with AF and HF will be discussed in this paper.
  • 626
  • 16 Sep 2021
Topic Review
Atrial Fibrillation Diagnosis Measurements
Atrial Fibrillation (AF) is a heart rhythm disorder. Hence, AF diagnosis is based on measurements which reflect the activity of the heart. Detectable symptoms of the disease might not be present all the time. Therefore, the measurement duration is positively correlated with the AF detection rate. Suitable measurements include photoplethysmogram, electrocardiogram, and heart rate. The data volume, produced through long term measurement, mandates computer support to automate the AF detection task.
  • 1.1K
  • 30 Oct 2020
Topic Review
Atrial Fibrillation in the Structural Heart Disease Population
Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Patients with structural heart disease (SHD) are at an increased risk of developing this arrhythmia and are particularly susceptible to the deleterious hemodynamic effects it carries. Catheter ablation (CA) has emerged as a valuable strategy for rhythm control and is currently part of the standard care for symptomatic relief in patients with AF. 
  • 572
  • 27 Feb 2023
Topic Review
Atrial Fibrillation Pathogenesis
Electrical remodeling lies on impaired calcium handling, enhanced inwardly rectifying potassium currents, and gap junction perturbations. In addition, a wide array of profibrotic stimuli activates fibroblast to an increased extracellular matrix turnover via various intermediaries. Concomitant dysregulation of the autonomic nervous system and the humoral function of increased epicardial adipose tissue (EAT) are established mediators in the pathophysiology of AF. Local atrial lymphomononuclear cells infiltrate and increased inflammasome activity accelerate and perpetuate arrhythmia substrate. Finally, impaired intracellular protein metabolism, excessive oxidative stress, and mitochondrial dysfunction deplete atrial cardiomyocyte ATP and promote arrhythmogenesis. 
  • 599
  • 09 Oct 2021
Topic Review
Attachment Therapy
Attachment therapy (also called "the Evergreen model," "holding time," "rage-reduction," "compression therapy," "rebirthing," "corrective attachment therapy," and Coercive Restraint Therapy) is a pseudoscientific child mental health intervention intended to treat attachment disorders. It is found primarily in the United States, and much of it is centered in about a dozen clinics in Evergreen, Colorado, where Foster Cline, one of the founders, established his clinic in the 1970s. The practice has resulted in adverse outcomes for children, including at least six documented child fatalities. Since the 1990s there have been a number of prosecutions for deaths or serious maltreatment of children at the hands of "attachment therapists" or parents following their instructions. Two of the most well-known cases are those of Candace Newmaker in 2000 and the Gravelles in 2003. Following the associated publicity, some advocates of attachment therapy began to alter views and practices to be less potentially dangerous to children. This change may have been hastened by the publication of a Task Force Report on the subject in January 2006, commissioned by the American Professional Society on the Abuse of Children (APSAC) which was largely critical of attachment therapy. In April 2007, ATTACh, an organization originally set up by attachment therapists, formally adopted a White Paper stating its unequivocal opposition to the use of coercive practices in therapy and parenting, promoting instead newer techniques of attunement, sensitivity and regulation. Attachment therapy is primarily based on Robert Zaslow's rage-reduction therapy from the 1960s and '70s and on psychoanalytic theories about suppressed rage, catharsis, regression, breaking down of resistance and defence mechanisms. Zaslow, Tinbergen, Martha Welch and other early proponents used it as a treatment for autism, based on the now discredited belief that autism was the result of failures in the attachment relationship with the mother. This form of treatment differs significantly from evidence-based attachment-based therapies, talking psychotherapies such as attachment-based psychotherapy and relational psychoanalysis.
  • 1.5K
  • 14 Oct 2022
Topic Review
Attachment-Based Therapy (Children)
Attachment-based therapy applies to interventions or approaches based on attachment theory, originated by John Bowlby. These range from individual therapeutic approaches to public health programs to interventions specifically designed for foster carers. Although attachment theory has become a major scientific theory of socioemotional development with one of the broadest, deepest research lines in modern psychology, attachment theory has, until recently, been less clinically applied than theories with far less empirical support. This may be partly due to lack of attention paid to clinical application by Bowlby himself and partly due to broader meanings of the word 'attachment' used amongst practitioners. It may also be partly due to the mistaken association of attachment theory with the pseudo-scientific interventions misleadingly known as attachment therapy. The approaches set out below are examples of recent clinical applications of attachment theory by mainstream attachment theorists and clinicians and are aimed at infants or children who have developed or are at risk of developing less desirable, insecure attachment styles or an attachment disorder.
  • 631
  • 26 Oct 2022
Topic Review
Attention Deficit Hyperactivity Disorder
Attention-deficit Hyperactivity Disorder is one of the most common childhood mental health disorders, affecting about 5.6% of the population worldwide.
  • 559
  • 15 Jan 2022
Topic Review
Attention Deficit Hyperactivity Disorder (ADHD)
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity. ADHD impairments arise from irregularities primarily in dopamine (DA) and norepinephrine (NE) circuits within the prefrontal cortex.
  • 801
  • 17 Feb 2022
Topic Review
Atypical Antipsychotics and Metabolic Syndrome
Atypical antipsychotics (AAPs) are commonly prescribed medications to treat schizophrenia, bipolar disorders and other psychotic disorders. However, they might cause metabolic syndrome (MetS) in terms of weight gain, dyslipidemia, type 2 diabetes (T2D), and high blood pressure, which are responsible for reduced life expectancy and poor adherence. Importantly, there is clear evidence that early metabolic disturbances can precede weight gain, even if the latter still remains the hallmark of AAPs use. In fact, AAPs interfere profoundly with glucose and lipid homeostasis acting mostly on hypothalamus, liver, pancreatic β-cells, adipose tissue, and skeletal muscle. Their actions on hypothalamic centers via dopamine, serotonin, acetylcholine, and histamine receptors affect neuropeptides and 5′AMP-activated protein kinase (AMPK) activity, thus producing a supraphysiological sympathetic outflow augmenting levels of glucagon and hepatic glucose production. In addition, altered insulin secretion, dyslipidemia, fat deposition in the liver and adipose tissues, and insulin resistance become aggravating factors for MetS. In clinical practice, among AAPs, olanzapine and clozapine are associated with the highest risk of MetS, whereas quetiapine, risperidone, asenapine and amisulpride cause moderate alterations. The new AAPs such as ziprasidone, lurasidone and the partial agonist aripiprazole seem more tolerable on the metabolic profile. However, these aspects must be considered together with the differences among AAPs in terms of their efficacy, where clozapine still remains the most effective. Intriguingly, there seems to be a correlation between AAP’s higher clinical efficacy and increase risk of metabolic alterations. Finally, a multidisciplinary approach combining psychoeducation and therapeutic drug monitoring (TDM) is proposed as a first-line strategy to avoid the MetS. In addition, pharmacological treatments are discussed as well.
  • 655
  • 23 Mar 2021
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