Beyond the Synapse: and FMRP Molecular Mechanisms in the Nucleus.

(Fragile X messenger ribonucleoprotein 1), located on the X-chromosome, encodes the multi-functional FMR1 protein (FMRP), critical to brain development and function. Trinucleotide CGG repeat expansions at this locus cause a range of neurological disorders, collectively referred to as Fragile X-related conditions. The most well-known of these is Fragile X syndrome, a neurodevelopmental disorder associated with syndromic facial features, autism, intellectual disabilities, and seizures.

Cell-type-specific effects of autism-associated 15q duplication syndrome in the human brain.

Recurrent copy-number variation represents one of the most well-established genetic drivers in neurodevelopmental disorders, including autism spectrum disorder. Duplication of 15q11-q13 (dup15q) is a well-described neurodevelopmental syndrome that increases the risk of autism more than 40-fold. However, the effects of this duplication on gene expression and chromatin accessibility in specific cell types in the human brain remain unknown.

Cell-type-specific effects of autism-associated chromosome 15q11.2-13.1 duplications in human brain.

Recurrent copy number variation represents one of the most well-established genetic drivers in neurodevelopmental disorders, including autism spectrum disorder (ASD). Duplication of 15q11.2-13.

Glial dysregulation in the human brain in fragile X-associated tremor/ataxia syndrome.

Short trinucleotide expansions at the FMR1 locus are associated with the late-onset condition fragile X-associated tremor/ataxia syndrome (FXTAS), which shows very different clinical and pathological features from fragile X syndrome (associated with longer expansions), with no clear molecular explanation for these marked differences. One prevailing theory posits that the shorter, premutation expansion uniquely causes extreme neurotoxic increases in FMR1 mRNA (i.e.

Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability.

We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and, in some brains, reflected in vivo clonal expansions.

Caregiving of children with Down syndrome: impact on quality of life, stress, mental and oral health.

Aim: Parental caregivers of children with Down Syndrome (DS) have a greater burden of daily activities that may affect their health. The aim of this exploratory study was to evaluate the impact of caregiving of children with Down syndrome on parenting quality of life, stress, mental and oral health.

Methods: Fifty-four parental caregivers of children with DS and 51 parents of children without physical or mental disabilities participated of this study.

Whole-genome analysis reveals the contribution of non-coding de novo transposon insertions to autism spectrum disorder.

Background: Retrotransposons have been implicated as causes of Mendelian disease, but their role in autism spectrum disorder (ASD) has not been systematically defined, because they are only called with adequate sensitivity from whole genome sequencing (WGS) data and a large enough cohort for this analysis has only recently become available.

Results: We analyzed WGS data from a cohort of 2288 ASD families from the Simons Simplex Collection by establishing a scalable computational pipeline for retrotransposon insertion detection. We report 86,154 polymorphic retrotransposon insertions-including > 60% not previously reported-and 158 de novo retrotransposition events.

Depression Impairs Level of Functioning in Chronic Kidney Disease Inpatients: A Case-Control Study.

Objectives To evaluate the difference in demographics and clinical correlates during hospitalization for chronic kidney disease (CKD) between patients with depression and those without depression, and its impact on the severity of illness and in-hospital mortality. Methods We conducted a case-control study and included 2,296 adult inpatients (age ≥18 years) with a primary discharge diagnosis of CKD using the nationwide inpatient sample (NIS). We used propensity score matching to extract the cases i.

Psychiatric Comorbidities in Pediatric Inpatients With Human Immunodeficiency Virus Infection and Impact on Hospital Course: Inputs From a Case-Control Inpatient Study.

Objectives In this study, we aimed to delineate psychiatric comorbidities in pediatric inpatients with versus without human immunodeficiency virus (HIV) infection and to measure its impact on the length of stay (LOS) and cost of treatment during hospitalization. Methodology We conducted a case-control study using the Nationwide Inpatient Sample and included 4,920 pediatric inpatients between the ages of six and 18 years who were sub-grouped by a comorbid diagnosis of HIV (N = 2,595) and non-HIV (N = 2,325) and matched for demographics (age, sex, and race) by propensity case-control matching. Logistic regression analyses were used to evaluate the adjusted odds ratio (aOR) of association for psychiatric comorbidities (depression, anxiety, post-traumatic stress disorder, psychosis, and drug abuse) in the HIV-positive compared with the HIV-negative (as reference category) pediatric inpatients.

Constraint Induced Movement Therapy Increases Functionality and Quality of Life after Stroke.

This blind randomized clinical trial evaluated the effect of CIMT on the functionality and quality of life (QOL) of chronic hemiparetics. Thirty volunteers were divided into two groups: Control (CG) and CIMT (CIMTG); evaluated before and after 12 and 24 intervention sessions. The scales used were: adapted Fugl-Meyer Motor Assessment (FMA), Modified Ashworth, Stroke Specific Quality Of Life (SS-QOL) and the Functional Reach Test (FRT).

Large mosaic copy number variations confer autism risk.

Although germline de novo copy number variants (CNVs) are known causes of autism spectrum disorder (ASD), the contribution of mosaic (early-developmental) copy number variants (mCNVs) has not been explored. In this study, we assessed the contribution of mCNVs to ASD by ascertaining mCNVs in genotype array intensity data from 12,077 probands with ASD and 5,500 unaffected siblings. We detected 46 mCNVs in probands and 19 mCNVs in siblings, affecting 2.

Influence of a glycolic acid-based final irrigant for photosensitizer removal of photodynamic therapy on the microhardness and colour change of the dentin structure.

Introduction: This study aimed to evaluate the influence of glycolic acid-based final irrigant for photosensitizer removal of photodynamic therapy on the microhardness and colour change of the dentin structure.

Methods: Eighty extracted single-rooted human incisors were used. Sample preparation and root split resulted in 160 samples, 80 samples being used for microhardness and 80 samples for colour change evaluation.

Recent Advances in Understanding the Genetic Architecture of Autism.

Recent advances in understanding the genetic architecture of autism spectrum disorder have allowed for unprecedented insight into its biological underpinnings. New studies have elucidated the contributions of a variety of forms of genetic variation to autism susceptibility. While the roles of de novo copy number variants and single-nucleotide variants-causing loss-of-function or missense changes-have been increasingly recognized and refined, mosaic single-nucleotide variants have been implicated more recently in some cases.

Association of calcium hypochlorite, reciprocating instrumentation and photodynamic therapy: Antimicrobial analysis and effects on root dentin structure.

Introduction: This study aimed to evaluate the antimicrobial action of calcium hypochlorite(Ca[OCl]) and sodium hypochlorite (NaOCl) with reciprocating instrumentation and photodynamic therapy(PDT), and its influence on root dentin structure.

Methods: One hundred and ten human teeth were used to antimicrobial evaluation, inoculated with Enterococcus faecalis and divided into 11 groups (n = 10): G1 - distilled water(control); G2-1 % NaOCl; G3-5.25 % NaOCl; G4-1 % Ca(OCl); G5-5.

Homozygous Missense Variants in NTNG2, Encoding a Presynaptic Netrin-G2 Adhesion Protein, Lead to a Distinct Neurodevelopmental Disorder.

NTNG2 encodes netrin-G2, a membrane-anchored protein implicated in the molecular organization of neuronal circuitry and synaptic organization and diversification in vertebrates. In this study, through a combination of exome sequencing and autozygosity mapping, we have identified 16 individuals (from seven unrelated families) with ultra-rare homozygous missense variants in NTNG2; these individuals present with shared features of a neurodevelopmental disorder consisting of global developmental delay, severe to profound intellectual disability, muscle weakness and abnormal tone, autistic features, behavioral abnormalities, and variable dysmorphisms. The variants disrupt highly conserved residues across the protein.

Reduced nucleus accumbens enkephalins underlie vulnerability to social defeat stress.

Enkephalins, endogenous ligands for delta opioid receptors (DORs), are highly enriched in the nucleus accumbens (NAc). They are implicated in depression but their role in the NAc, a critical brain region for motivated behavior, is not fully investigated. To provide insight into enkephalin function we used a chronic social defeat stress paradigm, where animals are either categorized as susceptible or resilient to stress based on their performance in a social interaction test.

Effects of Eccentric-Focused Versus Conventional Training on Lower Limb Muscular Strength in Older People: A Systematic Review With Meta-Analysis.

Eccentric-focused training promotes greater gains in muscle strength compared to other types of training in adults. However, for older people, these findings are still not well understood. A systematic review and meta-analysis were performed using manuscripts that performed eccentric-focused (ET) and conventional resistance training (CT) at least four weeks and evaluated maximum muscle strength through tests of maximum repetitions in weight machine exercises (knee extension and leg press exercises).

Influence of final irrigation protocols and endodontic sealer on bond strength of root filling material with root dentin previously treated with photodynamic therapy.

Introduction: The aim of this study was to evaluate the influence of final irrigation protocols and endodontic sealer on bond strength of root filling material on root dentin previously treated with photodynamic therapy (PDT).

Methods: One hundred root canals were prepared up to #F3 file of Pro-Taper system to receive the root filling material. All samples were submitted to PDT and randomly divided into five groups (n = 20) according to final irrigation protocols: Group 1-distilled water + ultrasonic activation (US); Group 2-17% EDTA; Group 3-QMix; Group 4-17% EDTA + US; Group 5-QMix + US.

Impaired mechanical properties of Achilles tendon in spastic stroke survivors: an observational study.

Background: The spasticity could lead to decreased functional capacity and changes in musculoskeletal tissue.

Objective: To compare the Achilles tendon properties between the affected and contralateral limbs of participants with spasticity due to stroke and the healthy subjects.

Methods: Fifteen individuals with ankle spasticity due to stroke and 15 healthy subjects were recruited.