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Topic Review
Copper Imbalance in Alzheimer’s Disease
Evidence indicates that patients with Alzheimer’s dementia (AD) show signs of copper (Cu) dyshomeostasis. This study aimed at evaluating the potential of Cu dysregulation as an AD susceptibility factor. We performed a meta-analysis of 56 studies investigating Cu biomarkers in brain specimens (pooled total of 182 AD and 166 healthy controls, HC) and in serum/plasma (pooled total of 2929 AD and 3547 HC). We also completed a replication study of serum Cu biomarkers in 97 AD patients and 70 HC screened for rs732774 and rs1061472 ATP7B, the gene encoding for the Cu transporter ATPase7B. Our meta-analysis showed decreased Cu in AD brain specimens, increased Cu and nonbound ceruloplasmin (Non-Cp) Cu in serum/plasma samples, and unchanged ceruloplasmin. Serum/plasma Cu excess was associated with a three to fourfold increase in the risk of having AD. Our replication study confirmed meta-analysis results and showed that carriers of the ATP7B AG haplotype were significantly more frequent in the AD group. Overall, our study shows that AD patients fail to maintain a Cu metabolic balance and reveals the presence of a percentage of AD patients carrying ATP7B AG haplotype and presenting Non-Cp Cu excess, which suggest that a subset of AD subjects is prone to Cu imbalance. This AD subtype can be the target of precision medicine-based strategies tackling Cu dysregulation.
  • 1.0K
  • 12 Jul 2021
Topic Review
Metabolism in Retinopathy of Prematurity
Retinopathy of prematurity is defined as retinal abnormalities that occur during development as a consequence of disturbed oxygen conditions and nutrient supply after preterm birth. Both neuronal maturation and retinal vascularization are impaired, leading to the compensatory but uncontrolled retinal neovessel growth. Current therapeutic interventions target the hypoxia-induced neovessels but negatively impact retinal neurons and normal vessels. Emerging evidence suggests that metabolic disturbance is a significant and underexplored risk factor in the disease pathogenesis. Hyperglycemia and dyslipidemia correlate with the retinal neurovascular dysfunction in infants born prematurely. Nutritional and hormonal supplementation relieve metabolic stress and improve retinal maturation. Here we focus on the mechanisms through which metabolism is involved in preterm-birth-related retinal disorder from clinical and experimental investigations. We will review and discuss potential therapeutic targets through the restoration of metabolic responses to prevent disease development and progression.
  • 1.0K
  • 09 Nov 2021
Topic Review
Advanced Rectal Cancer
The response to neoadjuvant chemoradiation (nCRT) is a critical step in the management of locally advanced rectal cancer (LARC) patients. Only a minority of LARC patients responds completely to neoadjuvant treatments, thus avoiding invasive radical surgical resection. Moreover, toxic side effects can adversely affect patients’ survival. The difficulty in separating in advances responder from non-responder patients affected by LARC highlights the need for valid biomarkers that guide clinical decision-making. In this context, circulating tumor biomarkers (i.e., microRNAs, circulating tumor cells and cell-free nucleic acids), as well as single nucleotide polymorphisms (SNPs) associated with miRNAs (miR-SNPs)) seem to be promising candidates for predicting LARC prognosis and/or therapy response.
  • 1.0K
  • 09 Oct 2020
Topic Review
Insulin Resistance and NAFLD development
Insulin resistance (IR) is a condition in which insulin action is altered. In metabolic terms, IR represents the inability of a fixed amount of insulin to metabolize a known amount of glucose in an individual as compared to the general population. 
  • 1.0K
  • 12 Oct 2021
Topic Review
Cachexia
Cachexia is a multifactorial syndrome characterized by body weight loss, declining muscle mass and function, wasting, and inflammation of adipose tissues accompanied by metabolic disarrangement, anorexia, systemic inflammation, and insulin resistance. Cachexia is associated with several acute and chronic disease states such as cancer, chronic obstructive pulmonary disease (COPD), heart and kidney failure, and acquired and autoimmune diseases and also pharmacological treatments such as chemotherapy.
  • 1.0K
  • 25 Feb 2021
Topic Review
Host Immune System Interaction
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by variable clinical presentation that ranges from asymptomatic to fatal multi-organ damage. The site of entry and the response of the host to the infection aect the outcomes. The role of the upper airways and the nasal barrier in the prevention of infection is increasingly being recognized. Besides the epithelial lining and the local immune system, the upper airways harbor a community of microorganisms, or microbiota, that takes an active part in mucosal homeostasis and in resistance to infection. However, the role of the upper airway microbiota in COVID-19 is not yet completely understood and likely goes beyond protection from viral entry to include the regulation of the immune response to the infection. Herein, we discuss the hypothesis that restoring endogenous barriers and anti-inflammatory pathways that are defective in COVID-19 patients might represent a valid strategy to reduce infectivity and ameliorate clinical symptomatology.
  • 1.0K
  • 16 Dec 2020
Topic Review
Tularemia
Francisella tularensis (Ft) is the etiological agent of tularemia, a disease known for over 100 years in the northern hemisphere. Ft includes four subspecies, of which two are the etiologic agents of tularemia: Ft subsp. tularensis (Ftt) and Ft subsp. holarctica (Fth), mainly distributed in North America and the whole northern hemisphere, respectively.
  • 1.0K
  • 27 Jan 2021
Topic Review
EWSR1
EWSR1 belongs to the FET family of RNA-binding proteins including also Fused in Sarcoma (FUS), and TATA-box binding protein Associated Factor 15 (TAF15).
  • 1.0K
  • 07 Jul 2021
Topic Review
Diagnosis and Management of Achalasia
Achalasia is a rare neurodegenerative disorder causing dysphagia and is characterized by abnormal esophageal motor function as well as the loss of lower esophageal sphincter (LES) relaxation. The assessment and management of achalasia has significantly progressed in recent years due to the advances in high-resolution manometry (HRM) technology along with the improvements and innovations of therapeutic endoscopy procedures. The recent evolution of HRM technology with the inclusion of an adjunctive test, fluoroscopy, and EndoFLIP has enabled more precise diagnoses of achalasia to be made and the subgrouping into therapeutically meaningful subtypes.
  • 1.0K
  • 25 Aug 2021
Topic Review
Cystic fibrosis (CF)
Cystic fibrosis (CF) is a lifelong disorder affecting 1 in 3500 live births worldwide. It is a monogenetic autosomal recessive disease caused by loss-of-function mutations in the gene encoding the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR), the impairment of which leads to ionic disequilibria in exocrine organs.
  • 1.0K
  • 12 Jan 2021
Topic Review
Individualized Hemodynamic Management in Sepsis
Hemodynamic optimization remains the cornerstone of resuscitation in the treatment of sepsis and septic shock. Delay or inadequate management will inevitably lead to hypoperfusion, tissue hypoxia or edema, and fluid overload, leading eventually to multiple organ failure, seriously affecting outcomes. According to a large international survey (FENICE study), physicians frequently use inadequate indices to guide fluid management in intensive care units. Goal-directed and “restrictive” infusion strategies have been recommended by guidelines over “liberal” approaches for several years. Unfortunately, these “fixed regimen” treatment protocols neglect the patient’s individual needs, and what is shown to be beneficial for a given population may not be so for the individual patient. However, applying multimodal, contextualized, and personalized management could potentially overcome this problem.
  • 998
  • 12 Mar 2021
Topic Review
Obstructive Sleep Apnea (OSA)
OSA is a major primary sleep disorder characterized by repetitive nocturnal complete (apnea) or partial (hypopnea), collapses of the upper airway during sleep accompanied by oxyhemoglobin desaturation and/or electroencephalography (EEG) and vegetative arousals. Nocturnal OSA symptoms include sleep fragmentation, diminished amounts of slow wave and rapid eye movement (REM) sleep, nocturia and insomnia. 
  • 997
  • 29 Oct 2020
Topic Review
Molecular Characterization of MTUT
Muellerian-type tumors of the urinary tract (MTUT) were implemented in the 2016 WHO classification as an entity comprising clear cell adenocarcinomas (CCAs) and endometrioid adenocarcinomas (EAs) of the bladder/urinary tract . The histologically clear cell tumors were initially described as mesonephric adenocarcinomas by Konnak in 1973 and re-named as clear cell adenocarcinomas in 1985 by Young and Scully.
  • 996
  • 01 Jul 2021
Topic Review
Autophagy and Therapeutic Pancreatic Tumors
Pancreatic cancer remains a poor-outcome disease with mortality rates nearly identical to incidence rates. Autophagy is a key metabolic process involved in stress resistance both intrinsically in tumor cells, and extrinsically in the tumor microenvironment (TME). 
  • 995
  • 19 Apr 2022
Topic Review
Genetic Determinants in Severe Asthma
Asthma is a chronic respiratory disease usually characterized by inflammatory changes in the lower airways that requires long-term management.
  • 994
  • 28 Sep 2021
Topic Review
EDCs and Prostate Disease
Endocrine-disrupting chemicals (EDCs) belong to a heterogeneous class of environmental pollutants widely diffused in different aquatic and terrestrial habitats. This implies that humans and animals are continuously exposed to EDCs from different matrices and sources. Moreover, pollution derived from anthropic and industrial activities leads to combined exposure to substances with multiple mechanisms of action on the endocrine system and correlated cell and tissue targets. For this reason, specific organs, such as the prostate gland, which physiologically are under the control of hormones like androgens and estrogens, are particularly sensitive to EDC stimulation. It is now well known that an imbalance in hormonal regulation can cause the onset of various prostate diseases, from benign prostate hyperplasia to prostate cancer.
  • 992
  • 21 Oct 2021
Topic Review
P53 in Biliary Tract Cancers
Gemcitabine-based chemotherapy is the current standard treatment for biliary tract cancers (BTCs) and resistance to gemcitabine remains the clinical challenge. TP53 mutation has been shown to be associated with poor clinicopathologic characteristics and survival in patients with BTCs, indicating that p53 plays an important role in the treatment of these cancers.
  • 989
  • 06 Nov 2020
Topic Review
Chromatin and Cancer
A hallmark of cancers is uncontrolled cell proliferation, frequently associated with an underlying imbalance in gene expression. This transcriptional dysregulation observed in cancers is multifaceted and involves chromosomal rearrangements, chimeric transcription factors, or altered epigenetic marks. Traditionally, chromatin dysregulation in cancers has been considered a downstream effect of driver mutations. Disruption of this large-scale chromatin in proliferating cancerous cells in conventional chemotherapies induces DNA damage and provides a positive feedback loop for chromatin rearrangements and tumor diversification. Consequently, the surviving cells from these chemotherapies become tolerant to higher doses of the therapeutic reagents, which are significantly toxic to normal cells. Furthermore, the disorganization of chromatin induced by these therapies accentuates nuclear fragility, thereby increasing the invasive potential of these tumors.
  • 989
  • 29 Jan 2023
Topic Review
Neonatal Screening for MPS Disorders
Newborn screening enables the diagnosis of treatable disorders at the early stages, and because of its countless benefits, conditions have been continuously added to screening panels, allowing early intervention, aiming for the prevention of irreversible manifestations and even premature death. Mucopolysaccharidoses (MPS) are lysosomal storage disorders than can benefit from an early diagnosis, and thus are being recommended for newborn screening. They are multisystemic progressive disorders, with treatment options already available for several MPS types. MPS I was the first MPS disorder enrolled in the newborn screening (NBS) panel in the USA and a few other countries, and other MPS types are expected to be added. Very few studies about NBS for MPS in Latin America have been published so far.
  • 985
  • 27 Nov 2020
Topic Review
Monoclonal Antibodies and Airway Diseases
Monoclonal antibodies, biologics, are a relatively new treatment option for severe chronic airway diseases, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS).
  • 985
  • 25 Dec 2020
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