Excess Synaptojanin 1 Contributes to Place Cell Dysfunction and Memory Deficits in the Aging Hippocampus in Three Types of Alzheimer's Disease.

The phosphoinositide phosphatase synaptojanin 1 (SYNJ1) is a key regulator of synaptic function. We first tested whether SYNJ1 contributes to phenotypic variations in familial Alzheimer's disease (FAD) and show that SYNJ1 polymorphisms are associated with age of onset in both early- and late-onset human FAD cohorts. We then interrogated whether SYNJ1 levels could directly affect memory.

New insights into the pharmacogenomics of antidepressant response from the GENDEP and STAR*D studies: rare variant analysis and high-density imputation.

Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (SNP), gene and pathway levels.

No evidence for the presence of genetic variants predisposing to psychotic disorders on the non-deleted 22q11.2 allele of VCFS patients.

The velo-cardio-facial syndrome (VCFS) is caused by hemizygous deletions on chromosome 22q11.2. The VCFS phenotype is complex and characterized by frequent occurrence of neuropsychiatric symptoms with up to 25-30% of cases suffering from psychotic disorders compared with only ~1% in the general population (odds ratio≈20-25).

Down syndrome and the complexity of genome dosage imbalance.

Down syndrome (also known as trisomy 21) is the model human phenotype for all genomic gain dosage imbalances, including microduplications. The functional genomic exploration of the post-sequencing years of chromosome 21, and the generation of numerous cellular and mouse models, have provided an unprecedented opportunity to decipher the molecular consequences of genome dosage imbalance. Studies of Down syndrome could provide knowledge far beyond the well-known characteristics of intellectual disability and dysmorphic features, as several other important features, including congenital heart defects, early ageing, Alzheimer disease and childhood leukaemia, are also part of the Down syndrome phenotypic spectrum.

Predictors of RSV LRTI Hospitalization in Infants Born at 33 to 35 Weeks Gestational Age: A Large Multinational Study (PONI).

Background: Preterm infants are at high risk of developing respiratory syncytial virus (RSV)-associated lower respiratory tract infection (LRTI). This observational epidemiologic study evaluated RSV disease burden and risk factors for RSV-associated LRTI hospitalization in preterm infants 33 weeks+0 days to 35 weeks+6 days gestational age not receiving RSV prophylaxis.

Methods: Preterm infants ≤6 months of age during RSV season (1 October 2013-30 April 2014) were followed at 72 sites across 23 countries from September 2013-July 2014 (study period).

Galanin pathogenic mutations in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is a common epilepsy syndrome with a complex etiology. Despite evidence for the participation of genetic factors, the genetic basis of TLE remains largely unknown. A role for the galanin neuropeptide in the regulation of epileptic seizures has been established in animal models more than two decades ago.

Exome sequencing in 53 sporadic cases of schizophrenia identifies 18 putative candidate genes.

Schizophrenia (SCZ) is a severe, debilitating mental illness which has a significant genetic component. The identification of genetic factors related to SCZ has been challenging and these factors remain largely unknown. To evaluate the contribution of de novo variants (DNVs) to SCZ, we sequenced the exomes of 53 individuals with sporadic SCZ and of their non-affected parents.

Determinants of hepatitis A vaccine immunity in a cohort of human immunodeficiency virus-infected children living in Switzerland.

Vaccination in HIV-infected children is often less effective than in healthy children. The goal of this study was to assess vaccine responses to hepatitis A virus (HAV) in HIV-infected children. Children of the Swiss Mother and Child HIV Cohort Study (MoCHiV) were enrolled prospectively.

Testosterone replacement therapy in reversing "andropause": what is the proof-of-principle?

Abstract Testosterone replacement therapy is often equated with the macho male physique and virility and is viewed by some as an antiaging tonic. The growth in testosterone's reputation and its increased use by men of all ages has seemed to outpace the scientific evidences. This review will aim to examine the uncertainty regarding the nature and the clinical importance of the age-related reduction in the testosterone levels.

Reversing T cell immunosenescence: why, who, and how.

Immunosenescence is the term commonly used to describe the multifaceted phenomenon encompassing all changes occurring in the immune system during aging. It contributes to render older adults more prone to develop infectious disease and main age-related diseases. While age clearly imposes drastic changes in immune physiology, older adults have heterogeneous health and immune phenotypes.

Aging adults and seasonal influenza: does the vitamin d status (h)arm the body?

Vitamin D (VitD), although originally described as an essential hormone for bone and mineral homeostasis, appears to have an active role in regulating specific facets of human immunity. Indeed, VitD has been shown to have significant effects on cytokine production and lymphocyte proliferation. Evidence that VitD affects clearance of selected pathogens is supported by epidemiological and clinical data, while its coadministration with influenza vaccine in mice enhanced both mucosal and systemic antibody responses.

Comparison of the interobserver variability of 2 different methods of dietary assessment in a geriatric ward: a pilot study.

Background: Protein-energy malnutrition is highly prevalent in aged populations. Associated clinical, economic, and social burden is important. A valid screening method that would be robust and precise, but also easy, simple, and rapid to apply, is essential for adequate therapeutic management.

Interdisciplinary geriatric and psychiatric care reduces potentially inappropriate prescribing in the hospital: interventional study in 150 acutely ill elderly patients with mental and somatic comorbid conditions.

Background: Potentially inappropriate medications and prescription omissions (PO) are highly prevalent in older patients with mental comorbidities.

Objective: To evaluate the effect of interdisciplinary geriatric and psychiatric care on the appropriateness of prescribing.

Design: Prospective and interventional study.

Chromosome conformation capture uncovers potential genome-wide interactions between human conserved non-coding sequences.

Comparative analyses of various mammalian genomes have identified numerous conserved non-coding (CNC) DNA elements that display striking conservation among species, suggesting that they have maintained specific functions throughout evolution. CNC function remains poorly understood, although recent studies have identified a role in gene regulation. We hypothesized that the identification of genomic loci that interact physically with CNCs would provide information on their functions.

Immunosenescence: Implications for vaccination programmes in adults.

Vaccination is crucially important in preventing infection and protecting vulnerable population from infectious diseases. However, a multitude of changes in the immune system occurring with advancing age, termed immunosenescence, lead to limit the protective effects of vaccination in older adults. While it is widely believed that the current immunization strategies saves many lives, vaccine preventable infectious diseases (VPDs) still place a considerable burden, not only on older individuals, but also on the adult population and healthcare systems of developed countries.

A systematic enhancer screen using lentivector transgenesis identifies conserved and non-conserved functional elements at the Olig1 and Olig2 locus.

Finding sequences that control expression of genes is central to understanding genome function. Previous studies have used evolutionary conservation as an indicator of regulatory potential. Here, we present a method for the unbiased in vivo screen of putative enhancers in large DNA regions, using the mouse as a model.

Influenza vaccination in the face of immune exhaustion: is herd immunity effective for protecting the elderly?

At the start of the 21st century, seasonal influenza virus infection is still a major public health concern across the world. The recent body of evidence confirms that trivalent inactivated influenza vaccines (TIVs) are not optimal within the population who account for approximately 90% of all influenza-related death: elderly and chronically ill individuals regardless of age. With the ever increasing aging of the world population and the recent fears of any pandemic influenza rife, great efforts and resources have been dedicated to developing more immunogenic vaccines and strategies for enhancing protection in these higher-risk groups.

Potentially inappropriate prescribing including under-use amongst older patients with cognitive or psychiatric co-morbidities.

Objective: the study aimed to determine the prevalence of and risk factors for inappropriate prescribing (IP) and prescribing omission (PO) in elderly with mental co-morbidities.

Participants: One hundred fifty consecutive inpatients with mental co-morbidities hospitalised for acute medical illness (mean age 80 +/- 9, 70% of women) were considered for the study.

Measurements: IP and PO were prospectively identified according to STOPP/START criteria at hospital admission.

Early markers of prolonged hospital stay in demented inpatients: a multicentre and prospective study.

Background: Dementia is a serious, chronic, and costly public health problem. Prior studies have described dementia as increasing length of hospital stay, but so far no explanations have been proposed.

Methods: To identify early markers for prolonged hospital stay in demented elderly inpatients, 178 community-dwelling or institutionalized subjects aged 75+, hospitalized through an emergency department in 9 teaching hospitals in France, were analyzed.

Determinants of vaccine immunity in the cohort of human immunodeficiency virus-infected children living in Switzerland.

Background: Human immunodeficiency virus (HIV)-infected children are at increased risk of infections caused by vaccine preventable pathogens, and specific immunization recommendations have been issued.

Methods: A prospective national multicenter study assessed how these recommendations are followed in Switzerland and how immunization history correlates with vaccine immunity.

Results: Among 87 HIV-infected children (mean age: 11.

Frailty syndrome: a transitional state in a dynamic process.

Frailty has long been considered synonymous with disability and comorbidity, to be highly prevalent in old age and to confer a high risk for falls, hospitalization and mortality. However, it is becoming recognized that frailty may be a distinct clinical syndrome with a biological basis. The frailty process appears to be a transitional state in the dynamic progression from robustness to functional decline.

Functional genetic variation of human miRNAs and phenotypic consequences.

A large number of human protein-coding genes are finely regulated by one or more microRNAs. Members of this small noncoding RNA family have emerged as important post-transcriptional regulators of gene expression and are involved in a number of disease phenotypes. Variability in the human genome is extensive and includes the common and rare single nucleotide polymorphisms (SNPs) and copy number variations (CNVs).

Mapping of small RNAs in the human ENCODE regions.

The elucidation of the largely unknown transcriptome of small RNAs is crucial for the understanding of genome and cellular function. We report here the results of the analysis of small RNAs (< 50 nt) in the ENCODE regions of the human genome. Size-fractionated RNAs from four different cell lines (HepG2, HelaS3, GM06990, SK-N-SH) were mapped with the forward and reverse ENCODE high-density resolution tiling arrays.

Characterization of mouse Dactylaplasia mutations: a model for human ectrodactyly SHFM3.

SHFM3 is a limb malformation characterized by the absence of central digits. It has been shown that this condition is associated with tandem duplications of about 500 kb at 10q24. The Dactylaplasia mice display equivalent limb defects and the two corresponding alleles (Dac1j and Dac2j) map in the region syntenic with the duplications in SHFM3.

Natural gene-expression variation in Down syndrome modulates the outcome of gene-dosage imbalance.

Down syndrome (DS) is characterized by extensive phenotypic variability, with most traits occurring in only a fraction of affected individuals. Substantial gene-expression variation is present among unaffected individuals, and this variation has a strong genetic component. Since DS is caused by genomic-dosage imbalance, we hypothesize that gene-expression variation of human chromosome 21 (HSA21) genes in individuals with DS has an impact on the phenotypic variability among affected individuals.