Bi-allelic variants in RNF170 are associated with hereditary spastic paraplegia.

Alterations of Ca2+ homeostasis have been implicated in a wide range of neurodegenerative diseases. Ca2+ efflux from the endoplasmic reticulum into the cytoplasm is controlled by binding of inositol 1,4,5-trisphosphate to its receptor. Activated inositol 1,4,5-trisphosphate receptors are then rapidly degraded by the endoplasmic reticulum-associated degradation pathway. Mutations in genes encoding the neuronal isoform of the inositol 1,4,5-trisphosphate receptor (ITPR1) and genes involved in inositol 1,4,5-trisphosphate receptor degradation (ERLIN1, ERLIN2) are known to cause hereditary spastic paraplegia (HSP) and cerebellar ataxia. We provide evidence that mutations in the ubiquitin E3 ligase gene RNF170, which targets inositol 1,4,5-trisphosphate receptors for degradation, are the likely cause of autosomal recessive HSP in four unrelated families and functionally evaluate the consequences of mutations in patient fibroblasts, mutant SH-SY5Y cells and by gene knockdown in zebrafish. Our findings highlight inositol 1,4,5-trisphosphate signaling as a candidate key pathway for hereditary spastic paraplegias and cerebellar ataxias and thus prioritize this pathway for therapeutic interventions

Biallelic Loss-of-Function NDUFA12 Variants Cause a Wide Phenotypic Spectrum from Leigh/Leigh-Like Syndrome to Isolated Optic Atrophy

BACKGROUND: Biallelic loss-of-function NDUFA12 variants have hitherto been linked to mitochondrial complex I deficiency presenting with heterogeneous clinical and radiological features in nine cases only. OBJECTIVES: To fully characterize, both phenotypically and genotypically, NDUFA12-related mitochondrial disease. METHODS: We collected data from cases identified by screening genetic databases of several laboratories worldwide and systematically reviewed the literature. RESULTS: Nine unreported NDUFA12 cases from six pedigrees were identified, with presentation ranging from movement disorder phenotypes (dystonia and/or spasticity) to isolated optic atrophy. MRI showed basal ganglia abnormalities (n = 6), optic atrophy (n = 2), or was unremarkable (n = 1). All carried homozygous truncating NDUFA12 variants, three of which are novel. CONCLUSIONS: Our case series expands phenotype–genotype correlations in NDUFA12-associated mitochondrial disease, providing evidence of intra- and inter-familial clinical heterogeneity for the same variant. It confirms NDUFA12 variants should be included in the diagnostic workup of Leigh/Leigh-like syndromes – particularly with dystonia – as well as isolated optic atrophy

Mental health issues in unaccompanied refugee minors

Previous studies about unaccompanied refugee minors (URMs) showed that they are a highly vulnerable group who have greater psychiatric morbidity than the general population. This review focuses on mental health issues among URMs. Articles in databases PsycINFO, Medline and PubMed from 1998 to 2008 addressing this topic were reviewed. The literature had a considerable emphasis on the assessment of PTSD symptoms. Results revealed higher levels of PTSD symptoms in comparison to the norm populations and accompanied refugee minors. In several studies, age and female gender predicted or influenced PTSD symptoms. The existing literature only permits limited conclusions on this very hard to reach population. Future research should include the analysis of long-term outcomes, stress management and a more thorough analysis of the whole range of psychopathology. Additionally, the development of culturally sensitive norms and standardized measures for diverse ethnic groups is of great importance

Structural and Functional Changes of the Human Macula during Acute Exposure to High Altitude

Background: This study aimed to quantify structural and functional changes at the macula during acute exposure to high altitude and to assess their structure/function relationship. This work is related to the Tuebingen High Altitude Ophthalmology (THAO) study. Methodology/Principal Findings: Spectral domain optical coherence tomography and microperimetry were used to quantify changes of central retinal structure and function in 14 healthy subjects during acute exposure to high altitude (4559 m). High-resolution volume scans and fundus-controlled microperimetry of the posterior pole were performed in addition to best-corrected visual acuity (BCVA) measurements and assessment of acute mountain sickness. Analysis of measurements at altitude vs. baseline revealed increased total retinal thickness (TRT) in all four outer ETDRS grid subfields during acute altitude exposure (TRTouter = 2.8061.00 mm; mean change695%CI). This change was inverted towards the inner four subfields (TRT inner = 21.8960.97 mm) with significant reduction of TRT in the fovea (TRT foveal = 26.6260.90 mm) at altitude. BCVA revealed no significant difference compared to baseline (0.0660.08 logMAR). Microperimetry showed stable mean sensitivity in all but the foveal subfield (MSfoveal = 21.1260.68 dB). At baseline recordings before and.2 weeks after high altitude exposure, all subjects showed equal levels with no sign of persisting structural or functional sequels. Conclusions/Significance: During acute exposure to high altitude central retinal thickness is subject to minor, ye

Biallelic Loss‐of‐Function NDUFA12 Variants Cause a Wide Phenotypic Spectrum from Leigh/Leigh‐Like Syndrome to Isolated Optic Atrophy

Abstract: Background: Biallelic loss‐of‐function NDUFA12 variants have hitherto been linked to mitochondrial complex I deficiency presenting with heterogeneous clinical and radiological features in nine cases only. Objectives: To fully characterize, both phenotypically and genotypically, NDUFA12‐related mitochondrial disease. Methods: We collected data from cases identified by screening genetic databases of several laboratories worldwide and systematically reviewed the literature. Results: Nine unreported NDUFA12 cases from six pedigrees were identified, with presentation ranging from movement disorder phenotypes (dystonia and/or spasticity) to isolated optic atrophy. MRI showed basal ganglia abnormalities (n = 6), optic atrophy (n = 2), or was unremarkable (n = 1). All carried homozygous truncating NDUFA12 variants, three of which are novel. Conclusions: Our case series expands phenotype–genotype correlations in NDUFA12‐associated mitochondrial disease, providing evidence of intra‐ and inter‐familial clinical heterogeneity for the same variant. It confirms NDUFA12 variants should be included in the diagnostic workup of Leigh/Leigh‐like syndromes – particularly with dystonia – as well as isolated optic atrophy

Digital health and mobile health: a bibliometric analysis of the 100 most cited papers and their contributing authors

Aim: This study aimed to identify and analyze the top 100 most cited digital health and mobile health (m-health) publications. It could aid researchers in the identification of promising new research avenues, additionally supporting the establishment of international scientific collaboration between interdisciplinary research groups with demonstrated achievements in the area of interest. Methods: On 30th August, 2023, the Web of Science Core Collection (WOSCC) electronic database was queried to identify the top 100 most cited digital health papers with a comprehensive search string. From the initial search, 106 papers were identified. After screening for relevance, six papers were excluded, resulting in the final list of the top 100 papers. The basic bibliographic data was directly extracted from WOSCC using its “Analyze” and “Create Citation Report” functions. The complete records of the top 100 papers were downloaded and imported into a bibliometric software called VOSviewer (version 1.6.19) to generate an author keyword map and author collaboration map. Results: The top 100 papers on digital health received a total of 49,653 citations. Over half of them (n = 55) were published during 2013–2017. Among these 100 papers, 59 were original articles, 36 were reviews, 4 were editorial materials, and 1 was a proceeding paper. All papers were written in English. The University of London and the University of California system were the most represented affiliations. The USA and the UK were the most represented countries. The Journal of Medical Internet Research was the most represented journal. Several diseases and health conditions were identified as a focus of these works, including anxiety, depression, diabetes mellitus, cardiovascular diseases, and coronavirus disease 2019 (COVID-19). Conclusions: The findings underscore key areas of focus in the field and prominent contributors, providing a roadmap for future research in digital and m-health

“The Buoy”: Utilization of a low-threshold ambulatory setting for traumatized children and adolescents in Austria

Grundlagen Diese Untersuchung hatte zum Ziel, die Inanspruchnahme einer Ambulanz, welche niedrigschwellige, Trauma-fokussierte Kurzpsychotherapie für Kinder und Jugendliche anbietet, während der ersten sechs Jahre ihres Bestehens zu untersuchen. Methodik Wir führten eine retrospektive Analyse der Krankengeschichten aller zwischen 2001 und 2007 behandelten Patienten (n=2510) durch und dokumentierten demographische Daten, Gründe für die Behandlung, zuweisende Institution, Obsorge berechtigte Person oder Institution, die Anzahl der Kontakte, psychische oder körperliche Erkrankung eines Elternteils und verschriebene Medikation. Ergebnisse Die behandelten Patienten waren zwischen 1 und 17 Jahre alt, die Geschlechterverteilung war gleichmäßig. Häufigster Anlass für eine Kontaktaufnahme waren der Tod eines Verwandten, die Tatsache, Zeuge eines gewaltsamen Todes geworden zu sein oder andere Gewalterfahrungen. Die Inanspruchnahme durch Migranten stieg während des Untersuchungszeitraumes laufend an. Kinder aus Pflegefamilien suchten die Institution seltener als erwartet auf. Medikation wurde kaum verschrieben. Schlussfolgerungen Die intensive Nutzung dieser Institution zeigt deutlich den großen Bedarf an kurzfristiger akuter Traumatherapie für Kinder und Jugendliche. Bemühungen, leicht zugängliche Institutionen für traumatisierte Kinder und Jugendliche zur Verfügung zu stellen, sollten intensiviert werden.Background This investigation intended to assess the use of an outpatient clinic providing low-threshold, short-term trauma therapy for children and adolescents across the first 6 years of its existence. Methods A retrospective analysis of the records of all patients undergoing treatment in this institution between 2001 and 2007 (n=2510) has been performed. We evaluated demographic data, reason for contacting the unit, the referring person or institution, the person or institution in charge of the care and custody of the child, the number of contacts with the clinic, presence of physical or psychiatric illness of a parent, and medications prescribed. Results Ages of patients ranged from 1 to 17. Gender distribution was even. Having experienced the death of a relative, experienced violence, or having witnessed traumatic death were the main reasons for presentation. The utilization rates of immigrants rose throughout the observation period. Children from foster care were seen less frequently than expected. Medication was hardly prescribed. Conclusions Ample utilization of this institution clearly demonstrates the need for short-term acute outpatient trauma therapy for children and adolescents. Efforts to provide easily accessible institutions for youth who experience traumatic events should be stepped up.(VLID)342645

Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of human ARH3, the first eukaryotic protein-ADP-ribosylhydrolase

ADP-ribosylhydrolases catalyze the release of ADP-ribose from ADP-ribosylated proteins via hydrolysis of the glycosidic bond between ADP-ribose and a specific amino-acid residue in a target protein. Human ADP-ribosylhydrolase 3, consisting of 347 amino-acid residues, has been cloned and heterologously expressed in Escherichia coli, purified and crystallized in two different space groups. Preliminary X-ray diffraction studies yielded excellent diffraction data to a resolution of 1.6 A

Structure of Mouse ADP-ribosylhydrolase 3 (mARH3)

ADP-ribosylation is a reversible and covalent post-translational modification in which the attachment of ADP-ribose is catalyzed by ADP-ribosyltransferases and the removal of ADP-ribose is catalyzed by ADP-ribosylhydrolases. ADP-ribosylhydrolase 3 from mouse, consisting of 347 amino-acid residues, has been cloned, purified and crystallized. The three-dimensional structure has been resolved at a resolution of 1.8 A. The structure constitutes a compact all-alpha-helical protein with two Mg(2+) ions located in the active-site crevice. A structural comparison of mouse ADP-ribosylhydrolase 3 with its human orthologue shows a high degree of structural similarity. Furthermore, four prokaryotic proteins deposited in the PDB could be identified as being structurally related