Elevated soluble receptor for advanced glycation end product levels in patients with acute coronary syndrome and positive cardiac troponin I

Objectives High levels of soluble receptor for advanced glycation end products (sRAGE) have been shown to have an atheroprotective role; however, no data are available on this molecule in acute coronary syndromes (ACS). We evaluated sRAGE levels in patients with non-ST segment elevation ACS (NSTE-ACS) or with chronic stable angina. Methods We studied 265 patients, 190 of whom had NSTE-ACS and 75 had chronic stable angina. Results Plasma sRAGE values were comparable in the two groups (P= 0.19). However, in the patients with NSTEACS,sRAGE levels were significantly higher in patients with cardiac troponin-I (cTnI) of more than or equal to 0.04 lg/l compared with those with cTnI of less than 0.04 lg/l [758 pg/ml (493-1536 pg/ml) vs. 454 pg/ml (167-899 pg/ml); P = 0.0037]. A significant correlation(r= 0.323, P = 0.0045) was found between sRAGE and cTnI levels in patients with NSTE-ACS.Conclusion Plasma sRAGE levels are elevated in patients with NSTE-ACS with positive cTnI, suggesting that they could be related to myocardial cell damage

Sleep disturbances and behavioral symptoms in pediatric Sotos syndrome

Background: Sotos syndrome (SoS) is a rare overgrowth genetic disease caused by intragenic mutations or microdeletions of the NSD1 gene located on chromosome 5q35. SoS population might present cognitive impairment and a spectrum of behavioral characteristics, with a worse profile in patients with microdeletion. Although patients with SoS are known to have impaired sleep habits, very little data are available. The present study aimed to assess the prevalence of sleep disorders (SDs) in a pediatric cohort of patients with SoS and their correlation with neuropsychiatric profiles. Methods: We included patients with a SoS diagnosis and age &lt; 18 years; all patients underwent a comprehensive neuropsychological assessment, including evaluation of cognition, adaptive functions through the Adaptive Behavior Assessment System-Second Edition (ABAS-II), and behavioral problems using the Achenbach Child Behavior Checklist (CBCL) and Conners’ Parent Rating Scale-Revised (CPRS-R:L) questionnaire. To investigate the presence of SD parents, the Sleep Disturbance Scale for Children (SDSC) was completed. Results: Thirty-eight patients (M 61%, F 39%, mean age 11.1 ± 4.65 years) were included in the study. Although only two had a prior SD diagnosis, 71.1% (N = 27) exhibited pathological scores on SDSC. No statistically significant associations were found between positive SDSC results and genetic microdeletion, intellectual disability (ID), or other medical conditions/treatments. However, a positive correlation emerged between SDSC scores and Conners’ Global Index (p = 0.048) and Restless/Impulsive (p = 0.01) scores, CBCL externalizing (p = 0.02), internalizing (p = 0.01), and total scores (p = 0.05). Conversely, a negative linear relationship was observed between the SDSC score and the ABAS GAC and ABAS CAD scores (p = 0.025). Conclusion: We detected an SD in 71.1% of our sample, with a positive relation between SD and internalizing and externalizing symptom levels, especially hyperactivity and impulsivity. Our study demonstrated a high prevalence of SD in pediatric patients with SoS, highlighting that all patients should be screened for this problem, which has a great impact on the quality of life of patients and their families.</p

Role of IL-6/STAT3 Axis in Resistance to Cisplatin in Gastric Cancers

Gastric cancer, the second most common cause of death worldwide, is characterized by poor prognosis and low responsiveness to chemotherapy. Indeed, multidrug resistance, based mainly on cellular and molecular factors, remains one of the most limiting factors of the current approach to gastric cancer (GC) therapy. We employed a comprehensive gene expression analysis through data mining of publicly available databases to assess the role of the signal transducer and activator of transcription 3 (STAT3) in gastric cancer drug efficiency. It has been proposed that gastric cancer cells are less sensitive to these drugs because they develop resistance to these agents through activating alternative signalling pathways responsible for overcoming pharmacological inhibition. Our study evaluated the hypothesis that activating STAT3 signalling in response to cisplatin reduces the reaction to the drug. Consistent with this hypothesis, inhibition of interleukin 6 (IL-6)/STAT3 in combination therapy with cisplatin prevented both STAT3 activation and more lethality than induction by a single agent. The data suggest that the IL-6/STAT3 axis block associated with cisplatin treatment may represent a strategy to overcome resistance

Sleep disturbances and behavioral symptoms in pediatric Sotos syndrome

BackgroundSotos syndrome (SoS) is a rare overgrowth genetic disease caused by intragenic mutations or microdeletions of the NSD1 gene located on chromosome 5q35. SoS population might present cognitive impairment and a spectrum of behavioral characteristics, with a worse profile in patients with microdeletion. Although patients with SoS are known to have impaired sleep habits, very little data are available. The present study aimed to assess the prevalence of sleep disorders (SDs) in a pediatric cohort of patients with SoS and their correlation with neuropsychiatric profiles.MethodsWe included patients with a SoS diagnosis and age &lt; 18 years; all patients underwent a comprehensive neuropsychological assessment, including evaluation of cognition, adaptive functions through the Adaptive Behavior Assessment System-Second Edition (ABAS-II), and behavioral problems using the Achenbach Child Behavior Checklist (CBCL) and Conners’ Parent Rating Scale-Revised (CPRS-R:L) questionnaire. To investigate the presence of SD parents, the Sleep Disturbance Scale for Children (SDSC) was completed.ResultsThirty-eight patients (M 61%, F 39%, mean age 11.1 ± 4.65 years) were included in the study. Although only two had a prior SD diagnosis, 71.1% (N = 27) exhibited pathological scores on SDSC. No statistically significant associations were found between positive SDSC results and genetic microdeletion, intellectual disability (ID), or other medical conditions/treatments. However, a positive correlation emerged between SDSC scores and Conners’ Global Index (p = 0.048) and Restless/Impulsive (p = 0.01) scores, CBCL externalizing (p = 0.02), internalizing (p = 0.01), and total scores (p = 0.05). Conversely, a negative linear relationship was observed between the SDSC score and the ABAS GAC and ABAS CAD scores (p = 0.025).ConclusionWe detected an SD in 71.1% of our sample, with a positive relation between SD and internalizing and externalizing symptom levels, especially hyperactivity and impulsivity. Our study demonstrated a high prevalence of SD in pediatric patients with SoS, highlighting that all patients should be screened for this problem, which has a great impact on the quality of life of patients and their families

Gastric Cancer Stem Cells: A Glimpse on Metabolic Reprogramming

Gastric cancer (GC) is one of the most widespread causes of cancer-related death worldwide. Recently, emerging implied that gastric cancer stem cells (GCSCs) play an important role in the initiation and progression of GC. This subpopulation comprises cells with several features, such as self-renewal capability, high proliferating rate, and ability to modify their metabolic program, which allow them to resist current anticancer therapies. Metabolic pathway intermediates play a pivotal role in regulating cell differentiation both in tumorigenesis and during normal development. Thus, the dysregulation of both anabolic and catabolic pathways constitutes a significant opportunity to target GCSCs in order to eradicate the tumor progression. In this review, we discuss the current knowledge about metabolic phenotype that supports GCSC proliferation and we overview the compounds that selectively target metabolic intermediates of CSCs that can be used as a strategy in cancer therapy

Candidate biomarkers from the integration of methylation and gene expression in discordant autistic sibling pairs

While the genetics of autism spectrum disorders (ASD) has been intensively studied, resulting in the identification of over 100 putative risk genes, the epigenetics of ASD has received less attention, and results have been inconsistent across studies. We aimed to investigate the contribution of DNA methylation (DNAm) to the risk of ASD and identify candidate biomarkers arising from the interaction of epigenetic mechanisms with genotype, gene expression, and cellular proportions. We performed DNAm differential analysis using whole blood samples from 75 discordant sibling pairs of the Italian Autism Network collection and estimated their cellular composition. We studied the correlation between DNAm and gene expression accounting for the potential effects of different genotypes on DNAm. We showed that the proportion of NK cells was significantly reduced in ASD siblings suggesting an imbalance in their immune system. We identified differentially methylated regions (DMRs) involved in neurogenesis and synaptic organization. Among candidate loci for ASD, we detected a DMR mapping to CLEC11A (neighboring SHANK1) where DNAm and gene expression were significantly and negatively correlated, independently from genotype effects. As reported in previous studies, we confirmed the involvement of immune functions in the pathophysiology of ASD. Notwithstanding the complexity of the disorder, suitable biomarkers such as CLEC11A and its neighbor SHANK1 can be discovered using integrative analyses even with peripheral tissues

The association of indwelling urinary catheter with delirium in hospitalized patients and nursing home residents: an explorative analysis from the "Delirium Day 2015"

Backround: Use of indwelling urinary catheter (IUC) in older adults has negative consequences, including delirium. Aim: This analysis, from the "Delirium Day 2015", a nationwide multicenter prevalence study, aim to evaluate the association of IUC with delirium in hospitalized and Nursing Homes (NHs) patients. Methods: Patients underwent a comprehensive geriatric assessment, including the presence of IUC; inclusion criteria were age &gt; 65 years, being Italian speaker and providing informed consent; exclusion criteria were coma, aphasia, end-of-life status. Delirium was assessed using the 4AT test (score ≥ 4: possible delirium; scores 1-3: possible cognitive impairment). Results: Among 1867 hospitalized patients (mean age 82.0 ± 7.5 years, 58% female), 539 (28.9%) had IUC, 429 (22.9%) delirium and 675 (36.1%) cognitive impairment. IUC was significantly associated with cognitive impairment (OR 1.60, 95% CI 1.19-2.16) and delirium (2.45, 95% CI 1.73-3.47), this latter being significant also in the subset of patients without dementia (OR 2.28, 95% CI 1.52-3.43). Inattention and impaired alertness were also independently associated with IUC. Among 1454 NHs residents (mean age 84.4 ± 7.4 years, 70.% female), 63 (4.3%) had IUC, 535 (36.8%) a 4AT score ≥ 4, and 653 (44.9%) a 4AT score 1-3. The multivariate logistic regression analysis did not show a significant association between 4AT test or its specific items with IUC, neither in the subset of patients without dementia. Discussion: We confirmed a significant association between IUC and delirium in hospitalized patients but not in NHs residents. Conclusion: Environmental and clinical factors of acute setting might contribute to IUC-associated delirium occurrence

&quot;Delirium Day&quot;: A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys