Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Orthodontic treatment of adult patients with mandibular retrognathia [Ortodonticheskoe lechenie vzroslykh patsientov s nizhnei retrognatiei]

This article describes a case report of the patient with mandibular retrognathia, class II malocclusion, constriction and deformation of dental arches and bimaxillary protrusion. Due to the patient's refuse to undergo the orthognathic surgery, after diagnostic, it was decided to carry out the orthodontic dentoalveolar compensation. The combined use of the functional fixed telescopic appliance (FFTA), bracket system and orthodontic miniscrews made it possible to effectively normalize the mandibular position, achieve orthognathic occlusion, eliminate bimaxillary protrusion and improve the face profile. This method significantly reduced invasiveness and time of orthodontic treatment.Представлен клинический случай пациентки со скелетной формой деформации челюстей, нижней ретрогнатией, дистальной окклюзией, сужением и деформацией зубоальвеолярных дуг и бипротрузией резцов. В связи с отказом пациентки от костно-реконструктивной операции после проведения комплексной диагностики приняли решение о применении ортодонтического лечения методом зубоальвеолярной компенсации. Комбинированное применение функционального несъемного телескопического аппарата (ФНТА), брекет-системы и ортодонтических миниимплантатов позволило эффективно нормализовать положение нижней челюсти, достичь ортогнатической окклюзии зубных рядов, устранить бипротрузию резцов и улучшить профиль лица. Такой метод позволил существенно снизить инвазивность и сократить продолжительность ортодонтического лечения

Algorithm for treatment of patients with class II malocclusion rejecting orthognathic surgery [Algoritm lecheniya patsientov s nizhnei retrognatiei, otkazavshikhsya ot kostno-rekonstruktivnoi operatsii]

The aim of this study is to develop algorithms for the treatment of patients with class II malocclusion and incisor protrusion using the combination of bracket system, functional fixed telescopic appliance (FFTA) and skeletal anchorage, which allows to achieve effective dentoalveolar compensation of skeletal forms of class II malocclusion. MATERIALS AND METHODS: Orthodontic treatment of 60 patients with class II malocclusion at the age of 18 to 44 years, using the bracket system, FFTA and orthodontic miniscrews was performed. In order to assess the results of treatment, cone-beam computed tomography were obtained at the beginning and at the end of treatment. RESULTS: As a result of the treatment normalization of lower jaw position, dental position and occlusion were achieved, the lower incisors protrusion was eliminated and the facial profile was improved, reliably confirmed by lateral cephalograms. CONCLUSION: The proposed treatment algorithm proved to be effective for stable correction of skeletal class II malocclusion in patients rejecting orthognathic surgery.ЦЕЛЬ ИССЛЕДОВАНИЯ: Разработка алгоритмов лечения пациентов с нижней ретрогнатией, дистальной окклюзией зубных рядов (ДОЗР) и протрузией резцов с помощью комбинированного применения несъемной ортодонтической техники и скелетной опоры, позволяющих эффективно проводить зубоальвеолярную компенсанцию скелетных форм дистальной окклюзии. МАТЕРИАЛ И МЕТОДЫ: Проведено ортодонтическое лечение 60 пациентов с нижней ретрогнатией и ДОЗР в возрасте от 18 до 44 лет при помощи брекет-системы, функционального несъемного телескопического аппарата (ФНТА) и ортодонтических минивинтов. С целью оценки результатов лечения каждому пациенту проводилось рентгенологическое исследование до и после лечения. РЕЗУЛЬТАТЫ: Было достигнуто улучшение соотношения челюстей по сагиттали, нормализовано положение нижней челюсти, нормализовано положение зубов и смыкание зубных рядов, устранена протрузия резцов и улучшен профиль лица, что достоверно подтверждено данными телерентгенографии черепа в боковой проекции. ЗАКЛЮЧЕНИЕ: Таким образом, разработанные нами алгоритмы лечения позволяют достичь стабильных результатов ортодонтической коррекции скелетных форм ДОЗР у пациентов, отказавшихся от ортогнатической хирургии

Comparative Assessment of The Expansion of The Dentition Using Ligature and Passive Self-Ligating Braces in Combination with Pitts Broad and Early Elastics

Background: The study aimed to analyze the effectiveness of the use of the Pitts Broad and early elastics in the treatment of patients with narrowing and deformation of the dentition. Materials and methods: A comprehensive examination of 46 patients, aged 18 to 30 years, with narrowing and deformation of the dentition was performed. Patients were separated into two groups, depending on the algorithm of treatment: group 1 - using the brackets of passive self-ligation, the Pitts Broad and early short elastics; group 2 - using ligature brackets and archwires Orthos. Results: Biometric analysis of the diagnostic models of the 1st group after treatment showed a significant expansion of maxillary arch between the premolars and molars (a distance between premolars: 39,8 +/- 0,4mm, between molars: 48,3 +/- 0,5mm) and mandibular arch (a distance between premolars: 37,1 +/- 0,5mm, between molars: 46,3 +/- 0,6mm) compared to the data before treatment. Biometric analysis of the diagnostic models of the 2nd group showed that expansion between the molars was achieved on a much smaller extent on both jaws, compared with the 1st group (maxilla: a distance between premolars - 35,7 +/- 0,4mm, between molars 43,5 +/- 0,5mm; mandible: a distance between premolars - 33,2 +/- 0,3mm, between molars - 42,3 +/- 0,5mm). Conclusions: As a result of the study, it was found that the passive self-ligation system in combination with a protocol of the Pitts Broad contributes to the expansion of dentition in aesthetically significant areas (distal regions) at the early stages of treatment. The use of early light elastics provides an early control of the premolars torque, and it allows us to achieve a balanced and wide smile at the end of treatment

FN3 protein fragment containing two type III fibronectin domains from B. longum GT15 binds to human tumor necrosis factor alpha in vitro

Most species of the genus Bifidobacterium contain the gene cluster PFNA, which is presumably involved in the species-specific communication between bacteria and their hosts. The gene cluster PFNA consists of five genes including fn3, which codes for a protein containing two fibronectin type III domains. Each fibronectin domain contains sites similar to cytokine-binding sites of human receptors. Based on this finding we assumed that this protein would bind specifically to human cytokines in vitro. We cloned a fragment of the fn3 gene (1503 bp; 501 aa) containing two fibronectin domains, from the strain B. longum subsp. longum GT15. After cloning the fragment into the expression vector pET16b and expressing it in E. coli, the protein product was purified to a homogenous state for further analysis. Using the immunoferment method, we tested the purified fragment's ability to bind the following human cytokines: IL-1β, IL-6, IL-10, TNFα. We developed a sandwich ELISA system to detect any specific interactions between the purified protein and any of the studied cytokines. We found that the purified protein fragment only binds to TNFα. © 2020 Elsevier Lt