Astrocyte transcriptomic analysis identifies glypican 5 downregulation as a contributor to synaptic dysfunction in Alzheimer's disease models.

Synaptic dysfunction is an early feature in Alzheimer's disease (AD) and correlates with cognitive decline. Astrocytes are essential regulators of synapses, impacting synapse formation, maturation, elimination and function. To understand if synapse-supportive functions of astrocytes are altered in AD, we used astrocyte BacTRAP mice to generate a comprehensive dataset of hippocampal astrocyte transcriptional alterations in two mouse models of Alzheimer's pathology (APPswe/PS1dE9 and Tau P301S), characterizing sex and age-dependent changes.

Tissue mosaicism, FMR1 expression and intellectual functioning in males with fragile X syndrome.

Fragile X syndrome (FXS) is caused by hypermethylation of the FMR1 promoter due to the full mutation expansion (full mutation [FM]: CGG ≥ 200 repeats) and silencing of FMR1. Assessment of mosaicism for active-unmethylated alleles has prognostic utility. This study examined relationships between FMR1 methylation in different tissues with FMR1 messenger ribonucleic acid (mRNA) and intellectual functioning in 87 males with FXS (1.

Histological inflammatory activity can predict endoscopic relapse in patients with ulcerative colitis who have achieved mucosal healing.

Background Aims: Current therapeutic goals in ulcerative colitis (UC) include clinical and endoscopic remission, named mucosal healing (MH). Despite MH, a proportion of patients suffer a clinical relapse, which has been related to histological inflammation. We aimed to identify which histopathological features or histopathological index cut-off was associated with endoscopic relapse (ER) in UC patients with MH.

Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis - An international cohort study.

Background: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP.

Methods: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018.

FMR1 mRNA from full mutation alleles is associated with ABC-C scores in males with fragile X syndrome.

Fragile X syndrome (FXS) is caused by a hypermethylated full mutation (FM) expansion with ≥ 200 CGG repeats, and a decrease in FMR1 mRNA and its protein. However, incomplete silencing from FM alleles has been associated with more severe autism features in FXS males. This study compared scores on the Aberrant Behavior Checklist-Community-FXS version (ABC-C) in 62 males affected with FXS (3 to 32 years) stratified based on presence or absence of mosaicism and/or FMR1 mRNA silencing.

Glia: victims or villains of the aging brain?

Aging is the strongest risk factor for metabolic, vascular and neurodegenerative diseases. Aging alone is associated with a gradual decline of cognitive and motor functions. Considering an increasing elderly population in the last century, understanding the cellular and molecular mechanisms contributing to brain aging is of vital importance.

Pathologist Experience and Concordance in the Diagnosis of Dysplasia in Long-standing Inflammatory Bowel Disease.

Surveillance colonoscopies focused to detect dysplasia are recommended to prevent colorectal cancer in patients with long-standing colonic inflammatory bowel disease (IBD). To date, histologic diagnosis and gradation of IBD-related dysplasia has been challenged by a high variability among pathologists. We aimed to analyze the observer characteristics that are correlated with concordance deviations in this diagnosis.

Intellectual functioning and behavioural features associated with mosaicism in fragile X syndrome.

Background: Fragile X syndrome (FXS) is a common cause of intellectual disability and autism spectrum disorder (ASD) usually associated with a CGG expansion, termed full mutation (FM: CGG ≥ 200), increased DNA methylation of the FMR1 promoter and silencing of the gene. Mosaicism for presence of cells with either methylated FM or smaller unmethylated pre-mutation (PM: CGG 55-199) alleles in the same individual have been associated with better cognitive functioning. This study compares age- and sex-matched FM-only and PM/FM mosaic individuals on intellectual functioning, ASD features and maladaptive behaviours.

Incomplete silencing of full mutation alleles in males with fragile X syndrome is associated with autistic features.

Background: Fragile X syndrome (FXS) is a common monogenic cause of intellectual disability with autism features. While it is caused by loss of the 1 product (FMRP), mosaicism for active and inactive alleles, including alleles termed premutation (PM: 55-199 CGGs), is not uncommon. Importantly, both PM and active full mutation (FM: ≥ 200 CGGs) alleles often express elevated levels of mRNA that are thought to be toxic.

Diabetes and Alzheimer's Disease: A Link not as Simple as it Seems.

Type 2 diabetes mellitus is associated with an increased risk to develop Alzheimer disease, however, the underlying mechanisms for this association are still unclear. In this review we will provide a critical overview of the major findings coming from clinical studies and animal models.

Increased Insoluble Amyloid-β Induces Negligible Cognitive Deficits in Old AppNL/NL Knock-In Mice.

Commonly used Alzheimer's disease mouse models are based on the ectopic overexpression of the human amyloid precursor protein (APP) gene, together with a mutant presenilin gene. Surprisingly, humanized APP knock-in mouse models carrying a single APP Swedish mutation (AppNL), failed to develop amyloid plaque aggregation or cognitive deficits. Here we characterized the effect of this mutation in more advanced ages.

High fat diet treatment impairs hippocampal long-term potentiation without alterations of the core neuropathological features of Alzheimer disease.

Type 2 diabetes (T2DM) and obesity might increase the risk for AD by 2-fold. Different attempts to model the effect of diet-induced diabetes on AD pathology in transgenic animal models, resulted in opposite conclusions. Here, we used a novel knock-in mouse model for AD, which, differently from other models, does not overexpress any proteins.

Correction: Tetraspanin 6: A novel regulator of hippocampal synaptic transmission and long term plasticity.

[This corrects the article DOI: 10.1371/journal.pone.

Correction: Tetraspanin 6: A novel regulator of hippocampal synaptic transmission and long term plasticity.

[This corrects the article DOI: 10.1371/journal.pone.

Tetraspanin 6: a pivotal protein of the multiple vesicular body determining exosome release and lysosomal degradation of amyloid precursor protein fragments.

Background: The mechanisms behind Aβ-peptide accumulation in non-familial Alzheimer's disease (AD) remain elusive. Proteins of the tetraspanin family modulate Aβ production by interacting to γ-secretase.

Methods: We searched for tetraspanins with altered expression in AD brains.

Tetraspanin 6: A novel regulator of hippocampal synaptic transmission and long term plasticity.

Tetraspanins (Tspan) are transmembrane proteins with important scaffold and signalling functions. Deletions of Tetraspanin 6 (Tspan6) gene, a member of the tetraspanin family, have been reported in patients with Epilepsy Female-restricted with Mental Retardation (EFMR). Interestingly, mutations in Tspan7, highly homologous to Tspan6, are associated with X-linked intellectual disability, suggesting that these two proteins are important for cognition.

FMR1 gene mutations in patients with fragile X syndrome and obligate carriers: 30 years of experience in Chile.

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID) and co-morbid autism. It is caused by an amplification of the CGG repeat (>200), which is known as the full mutation, within the 5'UTR of the FMR1 gene. Expansions between 55-200 CGG repeats are termed premutation and are associated with a greater risk for fragile X-associated tremor/ataxia syndrome and fragile X-associated premature ovarian insufficiency.

Identification of Males with Cryptic Fragile X Alleles by Methylation-Specific Quantitative Melt Analysis.

Background: FMR1 full mutations (FMs) (CGG expansion >200) in males mosaic for a normal (<45 CGG) or gray-zone (GZ) (45-54 CGG) allele can be missed with the standard 2-step fragile X syndrome (FXS) testing protocols, largely because the first-line PCR tests showing a normal or GZ allele are not reflexed to the second-line test that can detect FM.

Methods: We used methylation-specific quantitative melt analysis (MS-QMA) to determine the prevalence of cryptic FM alleles in 2 independent cohorts of male patients (994 from Chile and 2392 from Australia) referred for FXS testing from 2006 to 2013. All MS-QMA-positive cases were retested with commercial triplet primed PCR, methylation-sensitive Southern blot, and a methylation-specific EpiTYPER-based test.

Noncholesteatomatous Cyst of the Tympanic Membrane: A Nonpublished Entity?

Introduction. The presence of a serous cyst in the tympanic membrane implies the description of a new or unpublished entity based on our knowledge whose origin may be very unlikely explained on actual embryologic and anatomic background. Clinical Case.

Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents.

Cognitive decline is one of the many characteristics of aging. Reduced long-term potentiation (LTP) and long-term depression (LTD) are thought to be responsible for this decline, although the precise mechanisms underlying LTP and LTD dampening in the old remain unclear. We previously showed that aging is accompanied by the loss of cholesterol from the hippocampus, which leads to PI3K/Akt phosphorylation.

[Impact of strength training exercise on secondary prevention of childhood obesity; an intervention within the school system].

Introduction: The physical exercise is an important therapeutic tool to prevent and treat obesity, as well as reducing metabolic alterations and the risk of non-communicable diseases.

Objective: To evaluate the impact of a strength training exercise intervention within the school system, this includes muscular strength exercise, dietary education and psychological support in obese children.

Methods: We worked with 120 obese schoolchildren, between 8 and 13 years, recruited from 3 schools.

[Residual effect of muscle strength exercise in secondary prevention of children obesity].

Introduction: The high prevalence of the obesity in Chilean students (23,1%), necessitates the application of interventions that incorporate muscle strength exercise, as this shows great efficacy in obese children.

Objective: To evaluate the residual effect of muscle strength exercise on body fat, metabolic syndrome and physical fitness in obese schoolchildren.

Methods: The sample included 111 obese schoolchildren, between 8 and 13 years, of 3 schools in the city of Santiago.

Stem cells and bronchial stump healing.

Objective: Bronchial stump dehiscence is still the most feared complication for the thoracic surgeon, with mortality rates ranging from 25% to 75%. This study reports the histologic effect of adult stem cells in the healing process of the bronchial stump after lung resection.

Methods: A left pneumonectomy was performed in 36 Wistar rats.