Mental health professionals and telehealth in a rural setting: a cross sectional survey.

Background: Telehealth usage has been promoted in all settings but has been identified as a panacea to issues of access and equity in the rural context. However, uptake and widespread integration of telehealth across all parts of the health system has been slow, with a myriad of barriers documented, including in rural settings. The crisis of the COVID-19 pandemic, saw barriers rapidly overturned with the unprecedented and exponential rise in telehealth usage.

Anxiety-like behavior and anxiolytic treatment in the Rett syndrome natural history study.

Background: Rett syndrome (RTT) is a neurodevelopmental disorder most often related to a pathogenic variant in the X-linked MECP2 gene. Internalizing behaviors appear to be common, but standard methods of diagnosing anxiety are not readily applied in this population which typically has cognitive impairment and limited expressive language. This study aims to describe the frequency of anxiety-like behavior and anxiolytic treatments along with associated clinical features in individuals with RTT.

The development of highly potent and selective small molecule correctors of Z α-antitrypsin misfolding.

α1-antitrypsin deficiency is characterised by the misfolding and intracellular polymerisation of mutant α1-antitrypsin protein within the endoplasmic reticulum (ER) of hepatocytes. Small molecules that bind and stabilise Z α-antitrypsin were identified via a DNA-encoded library screen. A subsequent structure based optimisation led to a series of highly potent, selective and cellular active α1-antitrypsin correctors.

Development of a small molecule that corrects misfolding and increases secretion of Z α -antitrypsin.

Severe α -antitrypsin deficiency results from the Z allele (Glu342Lys) that causes the accumulation of homopolymers of mutant α -antitrypsin within the endoplasmic reticulum of hepatocytes in association with liver disease. We have used a DNA-encoded chemical library to undertake a high-throughput screen to identify small molecules that bind to, and stabilise Z α -antitrypsin. The lead compound blocks Z α -antitrypsin polymerisation in vitro, reduces intracellular polymerisation and increases the secretion of Z α -antitrypsin threefold in an iPSC model of disease.

Phenotypic features in MECP2 duplication syndrome: Effects of age.

Background: MECP2 Duplication syndrome (MDS) is a rare X-linked genomic disorder that is caused by interstitial chromosomal duplications at Xq28 encompassing the MECP2 gene. Although phenotypic features in MDS have been described, there is a limited understanding of the range of severity of these features, and how they evolve with age.

Methods: The cross-sectional results of N = 69 participants (ages 6 months-33 years) enrolled in a natural history study of MDS are presented.

Functional analysis of a novel mutation in the TIMM8A gene that causes deafness-dystonia-optic neuronopathy syndrome.

Background: The rare, X-linked neurodegenerative disorder, Mohr-Tranebjaerg syndrome (also called deafness-dystonia-optic neuronopathy [DDON] syndrome), is caused by mutations in the TIMM8A gene. DDON syndrome is characterized by dystonia, early-onset deafness, and various other neurological manifestations. The TIMM8A gene product localizes to the intermembrane space in mitochondria where it functions in the import of nuclear-encoded proteins into the mitochondrial inner membrane.

Characterizing the phenotypic effect of Xq28 duplication size in MECP2 duplication syndrome.

Individuals with methyl CpG binding protein 2 (MECP2) duplication syndrome (MDS) have varying degrees of severity in their mobility, hand use, developmental skills, and susceptibility to infections. In the present study, we examine the relationship between duplication size, gene content, and overall phenotype in MDS using a clinical severity scale. Other genes typically duplicated within Xq28 (eg, GDI1, RAB39B, FLNA) are associated with distinct clinical features independent of MECP2.

Scoliosis in Rett Syndrome: Progression, Comorbidities, and Predictors.

Background: Scoliosis is prominent in Rett syndrome (RTT). Following the prior report from the US Natural History Study, the onset and progression of severe scoliosis (≥40° Cobb angle) and surgery were examined regarding functional capabilities and specific genotypes, addressing the hypothesis that abnormal muscle tone, poor oral feeding, puberty, and delays or absence of sitting balance and ambulation may be responsible for greater risk in RTT.

Methods: The multicenter RTT Natural History Study gathered longitudinal data for classic RTT, including mutation type, scoliosis, muscle tone, sitting, ambulation, hand function, and feeding.

Assessment of Caregiver Inventory for Rett Syndrome.

Rett syndrome (RTT) requires total caregiver attention and leads to potential difficulties throughout life. The Caregiver Burden Inventory, designed for Alzheimer disease, was modified to a RTT Caregiver Inventory Assessment (RTT CIA). Reliability and face, construct, and concurrent validity were assessed in caregivers of individuals with RTT.

Importance of genetic testing in global health during the evaluation of familial microcephaly.

A focused genetic workup is useful in determining the cause of familial microcephaly, especially in the setting of mildly different phenotypes. As illustrated by this case from an impoverished international urban location, one must not assume the etiology for the apparent familial microcephaly is the same for all affected members.

Discovery and Characterization of a Class of Pyrazole Inhibitors of Bacterial Undecaprenyl Pyrophosphate Synthase.

Undecaprenyl pyrophosphate synthase (UppS) is an essential enzyme in bacterial cell wall synthesis. Here we report the discovery of Staphylococcus aureus UppS inhibitors from an Encoded Library Technology screen and demonstrate binding to the hydrophobic substrate site through cocrystallography studies. The use of bacterial strains with regulated uppS expression and inhibitor resistant mutant studies confirmed that the whole cell activity was the result of UppS inhibition, validating UppS as a druggable antibacterial target.

Rare Noncoding Mutations Extend the Mutational Spectrum in the PGAP3 Subtype of Hyperphosphatasia with Mental Retardation Syndrome.

HPMRS or Mabry syndrome is a heterogeneous glycosylphosphatidylinositol (GPI) anchor deficiency that is caused by an impairment of synthesis or maturation of the GPI-anchor. The expressivity of the clinical features in HPMRS varies from severe syndromic forms with multiple organ malformations to mild nonsyndromic intellectual disability. In about half of the patients with the clinical diagnosis of HPMRS, pathogenic mutations can be identified in the coding region in one of the six genes, one among them is PGAP3.

Caretaker Quality of Life in Rett Syndrome: Disorder Features and Psychological Predictors.

Objective: Rett syndrome is a severe neurodevelopmental disorder affecting approximately one in 10,000 female births. The clinical features of Rett syndrome are known to impact both patients' and caretakers' quality of life in Rett syndrome. We hypothesized that more severe clinical features would negatively impact caretaker physical quality of life but would positively impact caretaker mental quality of life.

Mucolipidosis type IV: a subtle pediatric neurodegenerative disorder.

The mucolipidoses are a heterogeneous group of autosomal recessive neurodegenerative lysosomal storage disorders. Mucolipidosis type IV is rare; it is seen predominantly in the Ashkenazi Jewish population and usually presents with global neurodevelopmental delays in infancy, subtle corneal opacifications or clouding, and very slowly progressive neurodegeneration over many years. Elevation of serum gastrin is reported; findings from x-rays of bone and joints and lysosomal studies are normal.

Longevity in Rett syndrome: analysis of the North American Database.

Objective: To determine longevity in Rett syndrome (RTT) from a large cohort.

Study Design: The North American RTT Database allows the examination of longevity in a large cohort of individuals with RTT from the United States and Canada. This database contains information on 1928 individuals, 85.

Rett syndrome: North American database.

The International Rett Syndrome Association (IRSA) North American database is the first comprehensive compilation of information in the United States and Canada on individuals with Rett syndrome or with another diagnosis in association with MECP2 mutations. The database contains specific information by diagnosis, mutation status, and mutation type and frequency on 1928 participants. Among the 1928 participants, 85.

Neuroprotection by encapsulated choroid plexus in a rodent model of Huntington's disease.

Choroid plexus from neonatal pigs was encapsulated in alginate microcapsules and transplanted into the rat striatum. Three days later, the same animals received unilateral injections of quinolinic acid (225 nmol) into the ipsilateral striatum. Choroid plexus transplants ameliorated the weight loss and motor impairments resulting from QA.

Intracerebral transplantation of porcine choroid plexus provides structural and functional neuroprotection in a rodent model of stroke.

Background And Purpose: Choroid plexus (CP) secretes a cocktail of neurotrophic factors. In the present study, CP from neonatal pigs was encapsulated within alginate microcapsules for in vitro and in vivo neuroprotective studies.

Methods: In vitro studies involved serum deprivation of rat embryonic cortical neurons and treatment with a range of concentrations of conditioned media from CP.

Does chromosome 22 have anything to do with sex determination: further studies on a 46,XX,22q11.2 del male.

Several years ago, we presented a patient with true hermaphroditism and partial duplication of chromosome 22 and no evidence of SRY (Aleck et al. [1999: Am J Med Genet 85:2-4]). Recently a 46,XX male with velocardiofacial syndrome and a deletion of 22q11.