A Mouse Model of the Human Fragile X Syndrome I304N Mutation

The mental retardation, autistic features, and behavioral abnormalities characteristic of the Fragile X mental retardation syndrome result from the loss of function of the RNA–binding protein FMRP. The disease is usually caused by a triplet repeat expansion in the 5′UTR of the FMR1 gene. This leads to loss of function through transcriptional gene silencing, pointing to a key function for FMRP, but precluding genetic identification of critical activities within the protein. Moreover, antisense transcripts (FMR4, ASFMR1) in the same locus have been reported to be silenced by the repeat expansion. Missense mutations offer one means of confirming a central role for FMRP in the disease, but to date, only a single such patient has been described. This patient harbors an isoleucine to asparagine mutation (I304N) in the second FMRP KH-type RNA–binding domain, however, this single case report was complicated because the patient harbored a superimposed familial liver disease. To address these issues, we have generated a new Fragile X Syndrome mouse model in which the endogenous Fmr1 gene harbors the I304N mutation. These mice phenocopy the symptoms of Fragile X Syndrome in the existing Fmr1–null mouse, as assessed by testicular size, behavioral phenotyping, and electrophysiological assays of synaptic plasticity. I304N FMRP retains some functions, but has specifically lost RNA binding and polyribosome association; moreover, levels of the mutant protein are markedly reduced in the brain specifically at a time when synapses are forming postnatally. These data suggest that loss of FMRP function, particularly in KH2-mediated RNA binding and in synaptic plasticity, play critical roles in pathogenesis of the Fragile X Syndrome and establish a new model for studying the disorder

One- and two-stage surgical revision of peri-prosthetic joint infection of the hip: a pooled individual participant data analysis of 44 cohort studies.

One-stage and two-stage revision strategies are the two main options for treating established chronic peri-prosthetic joint infection (PJI) of the hip; however, there is uncertainty regarding which is the best treatment option. We aimed to compare the risk of re-infection between the two revision strategies using pooled individual participant data (IPD). Observational cohort studies with PJI of the hip treated exclusively by one- or two-stage revision and reporting re-infection outcomes were retrieved by searching MEDLINE, EMBASE, Web of Science, The Cochrane Library, and the WHO International Clinical Trials Registry Platform; as well as email contact with investigators. We analysed IPD of 1856 participants with PJI of the hip from 44 cohorts across four continents. The primary outcome was re-infection (recurrence of infection by the same organism(s) and/or re-infection with a new organism(s)). Hazard ratios (HRs) for re-infection were calculated using Cox proportional frailty hazards models. After a median follow-up of 3.7 years, 222 re-infections were recorded. Re-infection rates per 1000 person-years of follow-up were 16.8 (95% CI 13.6-20.7) and 32.3 (95% CI 27.3-38.3) for one-stage and two-stage strategies respectively. The age- and sex-adjusted HR of re-infection for two-stage revision was 1.70 (0.58-5.00) when compared with one-stage revision. The association remained consistently absent after further adjustment for potential confounders. The HRs did not vary importantly in clinically relevant subgroups. Analysis of pooled individual patient data suggest that a one-stage revision strategy may be as effective as a two-stage revision strategy in treating PJI of the hip

<i>Cis</i> P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae

Induction of the cis form of phosphorylated tau (cis P-tau) has previously been shown to occur in animal models of traumatic brain injury (TBI), and blocking this form of tau using antibody was beneficial in a rodent model of severe TBI. Here the authors show that cis P-tau induction is a feature of several different forms of TBI in humans, and that administration of cis P-tau targeting antibody to rodents reduces or delays pathological features of TBI

Hydrillae

Progettazione di Housing Sociale: un quartiere di edilizia residenziale sociale integrata al borgo storico preesistente, al tessuto rurale, al sistema metropolitano ed infrastrutturale della periferia di Milan

Oncological Children and Well-Being: Occupational Performance and HRQOL Change after Fine Motor Skills Stimulation Activities

Cancer children experience long periods of hospitalization, which are associated with limited performance in several developmental domains and participation restrictions in age appropriate occupations. Fine motor abilities represent building blocks in performing daily life skills and have been found to be closely connected with later academic success. Moreover, medical and psychological sequelae for cancer inpatients may result in diminished daily activities functioning, poor perceived health related quality of life (HRQOL), and increase the likelihood of long-term impairments. This study examines the variations in the occupational performance of children hospitalized for acute lymphoblastic leukemia (ALL) after their participation to a stimulation program designed to enhance fine motor skills. Parents reported significant gains in children’s motor functioning, a slight improvement in overall occupational performance related to an increase in the area of productivity and self-care, and a better quality of life perception following the stimulation activities. Feasibility of the stimulation program in a health care setting are discussed evaluating its benefits for cancer children and their families

Plasma thiobarbituric acid reactive substances a predictive marker of cerebral ischemia in patients at high risk?

The clinical meaning of high values of blood lipid peroxides, assessed as thiobarbituric acid reactive substances (TBA-RS), was investigated in 19 selected high risk patients with transient ischemic attacks (TIA). Patients were checked every 3-6 months and followed-up for 3 years. 8 patients experienced further vascular episodes, 4 having minor stroke and 4 TIA; one of the latter died from myocardial infarction. Unlike blood cholesterol and glucose, TBA-RS values discriminated patients with vascular episodes: they, indeed, showed significant higher values of TBA-RS. Discriminant analysis further indicated that TBA-RS levels differentiate patients with and without vascular accidents, suggesting that high blood values of lipid peroxides could represent a predictive sign of vascular ischemia